Azaindoles

ABSTRACT

The invention is directed to compositions containing physiologically active compounds of general formula (I):  
                 
 
     wherein R 1  is aryl or heteroaryl; R 2  represents hydrogen, acyl, cyano, halo, lower alkenyl or lower alkyl optionally substituted by a substituent selected from cyano, heteroaryl, heterocycloalkyl, —Z 1 R 8 , —C(═O)—NY 3 Y 4 , —CO 2 R 8 , —NY 3 Y 4 , —N(R 6 )—C(═O)—R 7 , —N(R 6 )—C(═O)—NY 3 Y 4 , —N(R 6 )—C(═O)—OR 7 , —N(R 6 )—SO 2 —R 7 , —N(R 6 )—SO 2 —NY 3 Y 4  and one or more halogen a toms ; R 3  represents hydrogen, aryl, cyano, halo, heteroaryl, lower alkyl, —C(═O)—OR 5  or —C(═O)—NY 3 Y; and X 1  represents N, CH, C-halo, C—CN, C—R 7 , C—NY 3 Y 4 , C—OH, C—Z 2 R 7 , C—C(═O)—OR 5 , C—C(═O)—NY 3 Y 4 , C—N(R 8 )—C(═O)—R 7 , C—SO 2 —NY 3 Y 4 , C—N(R 8 )—SO 2 —R 7 , C-alkenyl, C-alkynyl or C—NO 2 ; and their prodrugs, and pharmaceutically acceptable salts and solvates of such compounds and their prodrugs, as well as to novel compounds within the scope of formula (I).  
     Such compounds and compositions have valuable pharmaceutical properties, in particular the ability to inhibit protein kinases.

[0001] This invention is directed to substituted azaindoles, theirpreparation, pharmaceutical compositions containing these compounds, andtheir pharmaceutical use in the treatment of disease states capable ofbeing modulated by the inhibition of the protein kinases.

[0002] Protein kinases participate in the signalling events whichcontrol the activation, growth and differentiation of cells in responseto extracellular mediators and to changes in the environment. Ingeneral, these kinases fall into several groups; those whichpreferentially phosphorylate serine and/or threonine residues and thosewhich preferentially phosphorylate tyrosine residues [S. K. Hanks and T.Hunter, FASEB. J., 1995, 9, pages 576-596]. The serine/threonine kinasesinclude for example, protein kinase C isoforms [A. C. Newton, J. Biol.Chem., 1995, 270, pages 28495-28498] and a group of cyclin-dependentkinases such as cdc2 [J. Pines, Trends in Biochemical Sciences, 1995,18, pages 195-197]. The tyrosine kinases include membrane-spanninggrowth factor receptors such as the epidermal growth factor receptor [S.Iwashita and M. Kobayashi, Cellular Signalling, 1992, 4, pages 123-132],and cytosolic non-receptor kinases such as p56tck, p59fYn, ZAP-70 andcsk kinases [C. Chan et. al., Ann. Rev. Immunol., 1994, l2, pages555-592].

[0003] Inappropriately high protein kinase activity has been implicatedin many diseases resulting from abnormal cellular function. This mightarise either directly or indirectly, for example by failure of theproper control mechanisms for the kinase, related for example tomutation, over-expression or inappropriate activation of the enzyme; orby over- or underproduction of cytokines or growth factors alsoparticipating in the transduction of signals upstream or downstream ofthe kinase. In all of these instances, selective inhibition of theaction of the kinase might be expected to have a beneficial effect.

[0004] Syk is a 72-kDa cytoplasmic protein tyrosine kinase that isexpressed in a variety of hematopoietic cells and is an essentialelement in several cascades that couple antigen receptors to cellularresponses. Thus, Syk plays a pivotal role in signalling of the highaffinity IgE receptor, FcεR1, in mast cells and in receptor antigensignalling in T and B lymphocytes. The signal transduction pathwayspresent in mast, T and B cells have common features. The ligand bindingdomain of the receptor lacks intrinsic tyrosine kinase activity.However, they interact with transducing subunits that containimmunoreceptor tyrosine based activation motifs (ITAMs) [M. Reth,Nature, 1989, 338, pages 383-384]. These motifs are present in both theβ and γ subunits of the FcεR1, in the ξ-subunit the of T cell receptor(TCR) and in the IgGα and IgG β subunits of the B cell receptor (BCR).[N. S. van Oers and A. Weiss, Seminars in Immunology, 1995, 7, pages227-236] Upon binding of antigen and multimerization, the ITAM residuesare phosphorylated by protein tyrosine kinases of the Src family. Sykbelongs to a unique class of tyrosine kinases that have two tandem Srchomology 2 (SH2) domains and a C terminal catalytic domain. These SH2domains bind with high affinity to ITAMs and this SH2 -mediatedassociation of Syk with an activated receptor stimulates Syk kinaseactivity and localises Syk to the plasma membrane.

[0005] In Syk deficient mice, mast cell degranulation is inhibited,suggesting that this is an important target for the development of mastcell stabilising agents [P. S. Costello, Oncogene, 1996, 13, pages2595-2605]. Similar studies have demonstrated a critical role for Syk inBCR and TCR signalling [A. M. Cheng, Nature, 1995, 378, pages 303-306,(1995) and D. H. Chu et al., Immunological Reviews, 1998, 165, pages167-180]. Syk also appears to be involved in eosinophil survival inresponse to IL-5 and GM-CSF [S. Yousefi et al., J. Exp. Med., 1996, 183,pages 1407-1414]. Despite the key role of Syk in mast cell, BCR and Tcell signalling, little is known about the mechanism by which Syktransmits downstream effectors. Two adaptor proteins, BLNK (B cellLinker protein, SLP-65) and SLP-76 have been shown to be substrates ofSyk in B cells and mast cells respectively and have been postulated tointerface Syk with downstream effectors [M. Ishiai et al., Immunity,1999, 10, pages 117-125 and L. R. Hendricks-Taylor et al., J.Biol. Chem,1997, 272, pages 1363-1367]. In addition Syk appears to play animportant role in the CD40 signalling pathway, which plays an importantrole in B cell proliferation [M. Faris et al., J.Exp. Med., 1994, 179,pages 1923-1931].

[0006] Syk is further involved in the activation of platelets stimulatedvia the low-affinity IgG receptor (Fc gamma-RIIA) or stimulated bycollagen [F. Yanaga et al., Biochem. J., 1995, 311, (Pt. 2) pages471-478].

[0007] Focal adhesion kinase (FAK) is a non-receptor tyrosine kinaseinvolved in integrin-mediated signal transduction pathways. FAKcolocalizes with integrins in focal contact sites and FAK activation andits tyrosine phosphorylation have been shown in many cell types to bedependent on integrins binding to their extracellular ligands. Resultsfrom several studies support the hypothesis that FAK inhibitors could beuseful in cancer treatment. For example, FAK-deficient cells migratepoorly in response to chemotactic signals and overexpression ofC-terminal domain of FAK blocks cell spreading as well as chemotacticmigration (Sieg et al, J. Cell Science,1999, 112, 2677-2691; RichardsonA. and Parsons T., Cell, 1997, 97, 221-231); in addition, tumor cellstreated with FAK antisense oligonucleotides lost their attachment andunderwent apoptosis (Xu et al, Cell Growth Differ. 1996, 4, 413-418).FAK has been reported to be overexpressed in prostate, breast, thyroid,colon and lung cancers. The level of expression of FAK is directlycorrelated with tumors demonstrating the most aggressive phenotype.

[0008] Angiogenesis or the formation of new blood vessels by sproutingfrom the preexisting vasculature is of central importance for embryonicdevelopment and organogenesis. Abnormal enhanced neovascularization isobserved in rheumatoid arthritis, diabetic retinopathy and during tumordevelopment (Folkman, Nat. Med., 1995, 1, 27-31.). Angiogenesis is acomplex multistage process which includes activation, migration,proliferation and survival of endothelial cells. Extensive studies inthe field of tumor angiogenesis in the past two decades have identifieda number of therapeutic targets including kinases, proteases andintegrins resulting in the discovery of many new anti-angiogenic agents,including KDR inhibitors some of which are currently under clinicalevaluation (Jekunen, et al Cancer Treatment Rev. 1997, 23, 263-286.).Angiogenesis inhibitors may be used in frontline, adjuvant and evenpreventive settings for the emergence or regrowth of malignancies.

[0009] Several proteins involved in chromosome segregation and spindleassembly have been identified in yeast and drosophila. Disruption ofthese proteins results in chromosome missegregation and monopolar ordisrupted spindles. Among these kinases are the Ipl1 and aurora kinasesfrom S. cerevisiae and drosophila respectively, which are required forcentrosome separation and chromosome segregation. One human homologue ofyeast Ipl1 was recently cloned and characterized by differentlaboratories. This kinase termed Aurora2, STK15 or BTAK belongs to theserine/threonine kinase family. Bischoff et al showed that Aurora2 isoncogenic and is amplified in human colorectal cancers (EMBO J, 1998,17, 3052-3065). It has also been exemplified in cancers involvingepithelial tumors such as breast cancer.

[0010] We have now found a novel group of substituted azaindoles, whichhave valuable pharmaceutical properties, in particular, the ability toinhibit protein kinases, more particularly, the ability to selectivelyinhibit Syk kinase.

[0011] Thus, in one aspect, the present invention is directed topharmaceutical compositions comprising compounds of general formula (I):

[0012] wherein:

[0013] R¹ represents aryl or heteroaryl each optionally substituted byone or more groups selected from acyl, alkylenedioxy, alkenyl,alkenyloxy, alkynyl, aryl, cyano, halo, hydroxy, heteroaryl,heterocycloalkyl, nitro, R⁴, —C(═O)—NY¹Y², —C(═O)—OR⁵, —NY¹Y²,—N(R⁶)—C(═O)—R⁷, —N(R⁶)—C(═O)—NY³Y⁴, —N(R⁶)—C(═O)—OR⁷, —N(R⁶)—SO₂—R⁷,—N(R⁶)—SO₂—NY³Y⁴, —SO₂—NY¹Y² and —Z²R⁴;

[0014] R² represents hydrogen, acyl, cyano, halo, lower alkenyl or loweralkyl optionally substituted by a substituent selected from cyano,heteroaryl, heterocycloalkyl, —Z¹R⁸, —C(═O)—NY³Y⁴, —CO₂R⁸, —NY³Y⁴,—N(R⁶)—C(═O)—R⁷, —N(R⁶)—C(═O)—NY³Y⁴, —N(R⁶)—C(═O)—OR⁷, —N(R⁶)—SO₂—R⁷,—N(R⁶)—SO₂—NY³Y⁴ and one or more halogen atoms;

[0015] R³ represents hydrogen, aryl, cyano, halo, heteroaryl, loweralkyl, —C(═O)—OR⁵ or —C(═O)—NY³Y;

[0016] R⁴ represents alkyl, cycloalkyl or cycloalkylalkyl eachoptionally substituted by a substituent selected from aryl, cycloalkyl,cyano, halo, heteroaryl, heterocycloalkyl, —CHO (or a 5-, 6- or7-membered cyclic acetal derivative thereof), —C(═O)—NY¹Y², —C(═O)—OR⁵,—NY¹Y², —N(R⁶)—C(═O)—R⁷, —N(R⁶)—C(═O)—NY³Y⁴, —N(R⁶)—SO₂—R⁷,—N(R⁶)—SO₂—NY³Y⁴, —OR⁷ and one or more groups selected from hydroxy andcarboxy;

[0017] R⁵ represents hydrogen, alkyl, alkenyl, aryl, arylalkyl,heteroaryl or heteroarylalkyl;

[0018] R⁶ represents hydrogen or lower alkyl;

[0019] R⁷ represents alkyl, aryl, arylalkyl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl orheterocycloalkylalkyl;

[0020] R⁸ represents hydrogen or lower alkyl;

[0021] X¹ represents N, CH, C-halo, C—CN, C—R⁷, C—NY³Y⁴, C—OH, C—Z²R⁷,C—C(═O)—OR⁵, C—C(═O)—NY³Y⁴, C—N(R⁸)—C(═O)—R⁷, C—SO₂—NY³Y⁴,C—N(R⁸)—SO₂—R⁷, C-alkenyl, C-alkynyl or C—NO₂;

[0022] Y¹ and Y² are independently hydrogen, alkenyl, aryl, cycloalkyl,heteroaryl or alkyl optionally substituted by one or more groupsselected from aryl, halo, heteroaryl, hydroxy, —C(═O)—NY³Y⁴, —C(═O)—OR⁵,—NY³Y⁴, —N(R⁶)—C(═O)—R⁷, —N(R⁶)—C(═O)—NY³Y⁴, —N(R⁶)—SO₂—R⁷,—N(R⁶)—SO₂—NY³Y⁴ and —OR⁷; or the group —NY¹Y² may form a cyclic amine;

[0023] Y³ and Y⁴ are independently hydrogen, alkenyl, alkyl, aryl,arylalkyl, cycloalkyl, heteroaryl or heteroarylalkyl; or the group—NY³Y⁴ may form a cyclic amine;

[0024] Z¹ represents O or S;

[0025] Z² represents O or S(O)_(n);

[0026] n is zero or an integer 1 or 2;

[0027] and their corresponding N-oxides, and their prodrugs, and theiracid bioisosteres; and

[0028] pharmaceutically acceptable salts and solvates (e.g. hydrates) ofsuch compounds and their N-oxides and their prodrugs, and their acidbioisosteres; together with one or more pharmaceutically acceptablecarriers or excipients.

[0029] In another aspect, the invention concerns the compounds offormula (I) as defined above, but excluding the compounds2-phenyl-1H-pyrrolo[2,3-b]pyridine,2-(4-bromo-phenyl)-3-methyl-1H-pyrrolo[2,3-b]pyridine,4-(3-methyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-benzoic acid methyl ester,2-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine,2-(4-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridine,5-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridine,4-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridine,2-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridine,4-(3-methyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-benzoic acid,2-(4-methoxy-phenyl)-3-methyl-1H-pyrrolo[2,3-b]pyridine,2-(4-methyl-phenyl)-3-methyl-1H-pyrrolo[2,3-b]pyridine,4-(3-methyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-benzoic acid isopropyl ester,2-phenyl-3-methyl-1H-pyrrolo[2,3-b]pyridine,5-bromo-2-phenyl-3-methyl-1H-pyrrolo[2,3-b]pyridine,6-chloro-2-phenyl-1H-pyrrolo[2,3-b]pyridine,6-chloro-4-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridine,4-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl-carboxaldehyde,2-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl-acetonitrile,2-phenyl-3-prop-1-enyl-1H-pyrrolo[2,3-b]pyridine,4-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl-carboxaldehyde,dimethyl-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-amine,2,2′-diphenyl-1H,1′H-[3,3′]bi[pyrrolo[2,3-b]pyridinyl],2-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-acetamide,3-allyl-2-phenyl-1H-pyrrolo[2,3-b]pyridine,(2-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-acetonitrile,2-phenyl-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde,3-morpholin-4-ylmethyl-2-phenyl-1H-pyrrolo[2,3-b]pyridine,N-[2-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-ethyl]-acetamide,6-phenyl-5H-pyrrolo[2,3-b]pyrazine,6-(4-methoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazine,6-(4-chloro-phenyl)-5H-pyrrolo[2,3-b]pyrazine,6-(2-chloro-phenyl)-5H-pyrrolo[2,3-b]pyrazine,3-methyl-6-phenyl-5H-pyrrolo[2,3-b]pyrazine,2-methyl-6-phenyl-5H-pyrrolo[2,3-b]pyrazine and7-methyl-6-phenyl-5H-pyrrolo[2,3-b]pyrazine.

[0030] In the present specification, the term “compounds of theinvention”, and equivalent expressions, are meant to embrace compoundsof general formula (I) as hereinbefore described, which expressionincludes the prodrugs, the pharmaceutically acceptable salts, and thesolvates, e.g. hydrates, where the context so permits. Similarly,reference to intermediates, whether or not they themselves are claimed,is meant to embrace their salts, and solvates, where the context sopermits. For the sake of clarity, particular instances when the contextso permits are sometimes indicated in the text, but these instances arepurely illustrative and it is not intended to exclude other instanceswhen the context so permits.

[0031] As used above, and throughout the description of the invention,the following terms, unless otherwise indicated, shall be understood tohave the following meanings:

[0032] “Patient” includes both human and other mammals.

[0033] “Acid bioisostere” means a group which has chemical and physicalsimilarities producing broadly similar biological properties to acarboxy group (see Lipinski, Annual Reports in Medicinal Chemistry,1986,21,p283 “Bioisosterism In Drug Design”; Yun, Hwahak Sekye, 1993,33, pages 576-579 “Application Of Bioisosterism To New Drug Design”;Zhao, Huaxue Tongbao, 1995, pages 34-38 “Bioisosteric Replacement AndDevelopment Of Lead Compounds In Drug Design”; Graham, Theochem, 1995,343, pages 105-109 “Theoretical Studies Applied To Drug Design:ab initioElectronic Distributions In Bioisosteres”). Examples of suitable acidbioisosteres include: —C(═O)—NHOH, —C(═O)—CH₂OH, —C(═O)—CH₂SH,—C(═O)—NH—CN, sulfo, phosphono, alkylsulfonylcarbamoyl, tetrazolyl,arylsulfonylcarbamoyl, heteroarylsulfonylcarbamoyl, N-methoxycarbamoyl,3-hydroxy-3-cyclobutene-1,2-dione, 3,5-dioxo-1,2,4-oxadiazolidinyl orheterocyclic phenols such as 3-hydroxyisoxazolyl and3-hydoxy-1-methylpyrazolyl.

[0034] “Acyl” means an H—CO— or alkyl-CO— group in which the alkyl groupis as described herein.

[0035] “Acylamino” is an acyl-NH— group wherein acyl is as definedherein.

[0036] “Alkenyl” means an aliphatic hydrocarbon group containing acarbon-carbon double bond and which may be straight or branched havingabout 2 to about 15 carbon atoms in the chain. Preferred alkenyl groupshave 2 to about 12 carbon atoms in the chain; and more preferably 2 toabout 6 carbon atoms (e.g. 2 to 4 carbon atoms) in the chain.“Branched,” as used herein and throughout the text, means that one ormore lower alkyl groups such as methyl, ethyl or propyl are attached toa linear chain; here a linear alkenyl chain. “Lower alkenyl” means about2 to about 4 carbon atoms in the chain, which may be straight orbranched. Exemplary alkenyl groups include ethenyl, propenyl, n-butenyl,i-butenyl, 3-methylbut-2-enyl, n-pentenyl, heptenyl, octenyl,cyclohexylbutenyl and decenyl.

[0037] “Alkenyloxy” is an alkenyl-O— group wherein alkenyl is as definedabove. Exemplary alkenyloxy groups include allyloxy.

[0038] “Alkoxy” means an alkyl-O— group in which the alkyl group is asdescribed herein. Exemplary alkoxy groups include difluoromethoxy,methoxy, trifluoromethoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy andheptoxy.

[0039] “Alkoxycarbonyl” means an alkyl-O—CO— group in which the alkylgroup is as described herein. Exemplary alkoxycarbonyl groups includemethoxy- and ethoxycarbonyl.

[0040] “Alkyl” means, unless otherwise specified, an aliphatichydrocarbon group which may be straight or branched chain having about 1to about 15 carbon atoms in the chain, optionally substituted by one ormore halogen atoms. Particular alkyl groups have from 1 to about 6carbon atoms. “Lower alkyl” as a group or part of a lower alkoxy, loweralkylthio, lower alkylsulfinyl or lower alkylsulfonyl group means unlessotherwise specified, an aliphatic hydrocarbon group which may be astraight or branched chain having 1 to about 4 carbon atoms in thechain. Exemplary alkyl groups include methyl, ethyl, n-propyl, i-propyl,n-butyl, s-butyl, t-butyl, n-pentyl, 3-pentyl, heptyl, octyl, nonyl,decyl and dodecyl. Exemplary alkyl groups substituted by one or morehalogen atoms include trifluoromethyl.

[0041] “Alkylene” means an aliphatic bivalent radical derived from astraight or branched alkyl group, in which the alkyl group is asdescribed herein. Exemplary alkylene radicals include methylene,ethylene and trimethylene.

[0042] “Alkylenedioxy” means an —O-alkylene-O— group in which alkyleneis as defined above. Exemplary alkylenedioxy groups includemethylenedioxy and ethylenedioxy.

[0043] “Alkylsulfinyl” means an alkyl-SO— group in which the alkyl groupis as previously described. Preferred alkylsulfinyl groups are those inwhich the alkyl group is C₁₋₄alkyl.

[0044] “Alkylsulfonyl” means an alkyl-SO₂— group in which the alkylgroup is as previously described. Preferred alkylsulfonyl groups arethose in which the alkyl group is C₁₋₄alkyl;

[0045] “Alkylsulfonylcarbamoyl” means an alkyl-SO₂—NH—C(═O)— group inwhich the alkyl group is as previously described. Preferredalkylsulfonylcarbamoyl groups are those in which the alkyl, group isC₁₋₄alkyl.

[0046] “Alkylthio” means an alkyl-S— group in which the alkyl group isas previously described. Exemplary alkylthio groups include methylthio,ethylthio, isopropylthio and heptylthio.

[0047] “Alkynyl” means an aliphatic hydrocarbon group containing acarbon-carbon triple bond and which group may be a straight or branchedchain having about 2 to about 15 carbon atoms in the chain. Preferredalkynyl groups have 2 to about 12 carbon atoms in the chain; and morepreferably 2 to about 6 carbon atoms (e.g. 2 to 4 carbon atoms) in thechain. Exemplary alkynyl groups include ethynyl, propynyl, n-butynyl,i-butynyl, 3-methylbut-2-ynyl, and n-pentynyl.

[0048] “Aroyl” means an aryl-CO— group in which the aryl group is asdescribed herein. Exemplary aroyl groups include benzoyl and 1- and2-naphthoyl.

[0049] “Aroylamino” is an aroyl-NH— group wherein aroyl is as previouslydefined.

[0050] “Aryl” as a group or part of a group denotes: (i) an optionallysubstituted monocyclic or multicyclic aromatic carbocyclic moiety ofabout 6 to about 14 carbon atoms, such as phenyl or naphthyl; or (ii) anoptionally substituted partially saturated multicyclic aromaticcarbocyclic moiety in which an aryl and a cycloalkyl or cycloalkenylgroup are fused together to form a cyclic structure, such as atetrahydronaphthyl, indenyl or indanyl ring. Except where otherwisedefined, aryl groups may be substituted with one or more aryl groupsubstituents, which may be the same or different, where “aryl groupsubstituent” includes, for example, acyl, acylamino, alkoxy,alkoxycarbonyl, alkylenedioxy, alkylsulfinyl, alkylsulfonyl, alkylthio,aroyl, aroylamino, aryl, arylalkyloxy, arylalkyloxycarbonyl,arylalkylthio, aryloxy, aryloxycarbonyl, arylsulfinyl, arylsulfonyl,arylthio, carboxy (or an acid bioisostere), cyano, halo, heteroaroyl,heteroaryl, heteroarylalkyloxy, heteroaroylamino, heteroaryloxy,hydroxy, nitro, trifluoromethyl, —NY³Y⁴, —CONY³Y⁴, —SO₂NY³Y⁴,—NY³—C(═O)alkyl, —NY³SO₂alkyl or alkyl optionally: substituted witharyl, heteroaryl, hydroxy, or —NY³Y⁴.

[0051] “Arylalkyl” means an aryl-alkyl- group in which the aryl andalkyl moieties are as previously described. Preferred arylalkyl groupscontain a C₁₋₄alkyl moiety. Exemplary arylalkyl groups include benzyl,2-phenethyl and naphthlenemethyl.

[0052] “Arylalkyloxy” means an arylalkyl-O— group in which the arylalkylgroups is as previously described. Exemplary arylalkyloxy groups includebenzyloxy and 1- or 2-naphthalenemethoxy.

[0053] “Arylalkyloxycarbonyl” means an arylalkyl-O—CO— group in whichthe arylalkyl groups is as previously described. An exemplaryarylalkyloxycarbonyl group is benzyloxycarbonyl.

[0054] “Arylalkylthio” means an arylalkyl-S— group in which thearylalkyl group is as previously described. An exemplary arylalkylthiogroup is benzylthio.

[0055] “Aryloxy” means an aryl-O— group in which the aryl group is aspreviously described. Exemplary aryloxy groups include phenoxy andnaphthoxy, each optionally substituted.

[0056] “Aryloxycarbonyl” means an aryl-O—C(═O)— group in which the arylgroup is as previously described. Exemplary aryloxycarbonyl groupsinclude phenoxycarbonyl and naphthoxycarbonyl.

[0057] “Arylsulfinyl” means an aryl-SO— group in which the aryl group isas previously described.

[0058] “Arylsulfonyl” means an aryl-SO₂— group in which the aryl groupis as previously described.

[0059] “Arylsulfonylcarbamoyl” means an aryl-SO₂—NH—C(═O)— group inwhich the aryl group is as previously described.

[0060] “Arylthio” means an aryl-S— group in which the aryl group is aspreviously described. Exemplary arylthio groups include phenylthio andnaphthylthio.

[0061] “Azaheteroaryl” means an aromatic carbocyclic moiety of about 5to about 10 ring members in which one of the ring members is nitrogenand the other ring members are selected from carbon, oxygen, sulfur, andnitrogen. Examples of azaheteroaryl groups include benzimidazolyl,imidazolyl, indazolinyl, indolyl, isoquinolinyl, pyridyl, pyrimidinyl,pyrrolyl, quinolinyl, quinazolinyl and tetrahydroindolizinyl.

[0062] “Cyclic amine” means a 3 to 8 membered monocyclic cycloalkyl ringsystem wherein one of the ring carbon atoms is replaced by nitrogen andwhich (i) may also contain a further heteroatom-containing groupselected from O, S, SO₂, or NY⁷ (where Y⁷ is hydrogen, alkyl, aryl,arylalkyl, —C(═O)—R⁷, —C(═O)—OR⁷ or —SO₂R⁷); and (ii) may be fused toadditional aryl (e.g. phenyl), heteroaryl (e.g. pyridyl),heterocycloalkyl or cycloalkyl rings to form a bicyclic or tricyclicring system. Exemplary cyclic amines include pyrrolidine, piperidine,morpholine, piperazine, indoline, pyrindoline, tetrahydroquinoline andthe like groups.

[0063] “Cycloalkenyl” means a non-aromatic monocyclic or multicyclicring system containing at least one carbon-carbon double bond and havingabout 3 to about 10 carbon atoms. Exemplary monocyclic cycloalkenylrings include cyclopentenyl, cyclohexenyl and cycloheptenyl.

[0064] “Cycloalkyl” means a saturated monocyclic or bicyclic ring systemof about 3 to about 10 carbon atoms, optionally substituted by oxo.Exemplary monocyclic cycloalkyl rings include C₃₋₈cycloalkyl rings suchas cyclopropyl, cyclopentyl, cyclohexyl and cycloheptyl.

[0065] “Cycloalkylalkyl” means a cycloalkyl-alkyl- group in which thecycloalkyl and alkyl moieties are as previously described. Exemplarymonocyclic cycloalkylalkyl groups include cyclopropylmethyl,cyclopentylmethyl, cyclohexylmethyl and cycloheptylmethyl.

[0066] “Halo” or “halogen” means fluoro, chloro, bromo, or iodo.Preferred are fluoro and chloro.

[0067] “Heteroaroyl” means a heteroaryl-C(═O)— group in which theheteroaryl group is as described herein. Exemplary heteroaryl groupsinclude pyridylcarbonyl.

[0068] “Heteroaroylamino” means a heteroaroyl-NH— group in which theheteroaryl moiety is as previously described.

[0069] “Heteroaryl” as a group or part of a group denotes: (i) anoptionally substituted aromatic monocyclic or multicyclic organic moietyof about 5 to about 10 ring members in which one or more of the ringmembers is/are element(s) other than carbon, for example nitrogen,oxygen or sulfur (examples of such groups include benzimidazolyl,benzthiazolyl, furyl, imidazolyl, indolyl, indolizinyl, isoxazolyl,isoquinolinyl, isothiazolyl, oxadiazolyl, pyrazinyl, pyridazinyl,pyrazolyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl,1,3,4-thiadiazolyl, thiazolyl, thienyl and triazolyl groups, optionallysubstituted by one or more aryl group substituents as defined aboveexcept where otherwise defined); (ii) an optionally substitutedpartially saturated multicyclic heterocarbocyclic moiety in which aheteroaryl and a cycloalkyl or cycloalkenyl group are fused together toform a cyclic structure (examples of such groups include pyrindanylgroups, optionally substituted by one or more “aryl group substituents”as defined above, except where otherwise defined). Optional substituentsinclude one or more “aryl group substituents” as defined above, exceptwhere otherwise defined.

[0070] “Heteroarylalkyl” means a heteroaryl-alkyl- group in which theheteroaryl and alkyl moieties are as previously described. Preferredheteroarylalkyl groups contain a C₁₋₄alkyl moiety. Exemplaryheteroarylalkyl groups include pyridylmethyl.

[0071] “Heteroarylalkyloxy” means an heteroarylalkyl-O— group in whichthe heteroarylalkyl group is as previously described. Exemplaryheteroaryloxy groups include optionally substituted pyridylmethoxy.

[0072] “Heteroaryloxy” means an heteroaryl-O— group in which theheteroaryl group is as previously described. Exemplary heteroaryloxygroups include optionally substituted pyridyloxy.

[0073] “Heteroarylsulfonylcarbamoyl” means a heteroaryl-SO₂—NH—C(═O)—group in which the heteroaryl group is as previously described.

[0074] “Heterocycloalkyl” means: (i) a cycloalkyl group of about 3 to 7ring members which contains one or more heteroatoms orheteroatom-containing groups selected from O, S and NY⁷ and mat beoptionally substituted by oxo; (ii) a partially saturated multicyclicheterocarbocyclic moiety in which an aryl (or heteroaryl) ring, eachoptionally substituted by one or more “aryl group substituents,” and aheterocycloalkyl group are fused together to form a cyclic structure.(Examples of such groups include chromanyl, dihydrobenzofuranyl,indolinyl and pyrindolinyl groups).

[0075] “Heterocycloalkylalkyl” means a heterocycloalkyl-alkyl- group inwhich the heterocycloalkyl and alkyl moieties are as previouslydescribed.

[0076] “Prodrug” means a compound which is convertible in vivo bymetabolic means (e.g. by hydrolysis) to a compound of formula (I),including N-oxides thereof. For example an ester of a compound offormula (I) containing a hydroxy group may be convertible by hydrolysisin vivo to the parent molecule. Alternatively, an ester of a compound offormula (I) containing a carboxy group may be convertible by hydrolysisin vivo to the parent molecule.

[0077] Suitable esters of compounds of formula (I) containing a hydroxygroup are, for example acetates, citrates, lactates, tartrates,malonates, oxalates, salicylates, propionates, succinates, fumarates,maleates, methylene-bis-β-hydroxynaphthoates, gentisates, isethionates,di-p-toluoyltartrates, methanesulfonates, ethanesulfonates,benzenesulfonates, p-toluenesulfonates, cyclohexylsulfamates andquinates.

[0078] Suitable esters of compounds of formula (I) containing a carboxygroup are, for example, those described by F. J. Leinweber, Drug Metab.Res., 1987, 18, page 379.

[0079] Suitable esters of compounds of formula (I) containing both acarboxy group and a hydroxy group within the moiety —L¹—Y includelactones formed by loss of water between said carboxy and hydroxygroups. Examples of such lactones include caprolactones andbutyrolactones.

[0080] An especially useful class of esters of compounds of formula (I)containing a hydroxy group, may be formed from acid moieties selectedfrom those described by Bundgaard et. al., J. Med. Chem., 1989, 32 ,page 2503-2507, and include substituted (aminomethyl)-benzoates, forexample dialkylamino-methylbenzoates in which the two alkyl groups maybe joined together and/or interrupted by an oxygen atom or by anoptionally substituted nitrogen atom, e.g. an alkylated nitrogen atom,more especially (morpholino-methyl)benzoates, e.g. 3- or4-(morpholinomethyl)-benzoates, and (4-alkylpiperazin-1-yl)benzoates,e.g. 3- or 4-(4-alkylpiperazin-1-yl)benzoates.

[0081] Where the compound of the invention contains a carboxy group, ora sufficiently acidic bioisostere, base addition salts may be formed andare simply a more convenient form for use; in practice, use of the saltform inherently amounts to use of the free acid form. The bases whichcan be used to prepare the base addition salts include preferably thosewhich produce, when combined with the free acid, pharmaceuticallyacceptable salts, that is, salts whose cations are non-toxic to thepatient in pharmaceutical doses of the salts, so that the beneficialinhibitory effects inherent in the free base are not vitiated by sideeffects ascribable to the cations. Pharmaceutically acceptable salts,including those derived from alkali and alkaline earth metal salts,within the scope of the invention include those derived from thefollowing bases: sodium hydride, sodium hydroxide, potassium hydroxide,calcium hydroxide, aluminium hydroxide, lithium hydroxide, magnesiumhydroxide, zinc hydroxide, ammonia, ethylenediamine, N-methyl-glucamine,lysine, arginine, ornithine, choline, N,N′-dibenzylethylenediamine,chloroprocaine, diethanolamine, procaine, N-benzylphenethylamine,diethylamine, piperazine, tris(hydroxymethyl)aminomethane,tetramethylammonium hydroxide, and the like.

[0082] Some of the compounds of the present invention are basic, andsuch compounds are useful in the form of the free base or in the form ofa pharmaceutically acceptable acid addition salt thereof.

[0083] Acid addition salts are a more convenient form for use; and inpractice, use of the salt form inherently amounts to use of the freebase form. The acids which can be used to prepare the acid additionsalts include preferably those which produce, when combined with thefree base, pharmaceutically acceptable salts, that is, salts whoseanions are non-toxic to the patient in pharmaceutical doses of thesalts, so that the beneficial inhibitory effects inherent in the freebase are not vitiated by side effects ascribable to the anions. Althoughpharmaceutically acceptable salts of said basic compounds are preferred,all acid addition salts are useful as sources of the free base form evenif the particular salt, per se, is desired only as an intermediateproduct as, for example, when the salt is formed only for purposes ofpurification, and identification, or when it is used as intermediate inpreparing a pharmaceutically acceptable salt by ion exchange procedures.Pharmaceutically acceptable salts within the scope of the inventioninclude those derived from mineral acids and organic acids, and includehydrohalides, e.g. hydrochlorides and hydrobromides, sulfates,phosphates, nitrates, sulfamates, acetates, citrates, lactates,tartrates, malonates, oxalates, salicylates, propionates, succinates,fumarates, maleates, methylene-bis-b-hydroxynaphthoates, gentisates,isethionates, di-p-toluoyltartrates, methane-sulfonates,ethanesulfonates, benzenesulfonates, p-toluenesulfonates,cyclohexylsulfamates and quinates.

[0084] As well as being useful in themselves as active compounds, saltsof compounds of the invention are useful for the purposes ofpurification of the compounds, for example by exploitation of thesolubility differences between the salts and the parent compounds, sideproducts and/or starting materials by techniques well known to thoseskilled in the art.

[0085] With reference to formula (I) above, the following are particularand preferred groupings:

[0086] R¹ may particularly represent optionally substituted heteroaryl,especially optionally substituted azaheteroaryl. Exemplary optionallysubstituted azaheteroaryls include indolyl, furanyl, pyridyl, pyrrolyl,pyrazolyl, quinolinyl, isoquinolinyl, imidazolyl, indazolyl,indolizinyl, tetrahydroindolizinyl and indazolinyl. Optionalsubstituents include one or more groups selected from alkylenedioxy,alkenyl, alkenyloxy, aryl, carboxy (or an acid bioisostere), cyano,halo, hydroxy, heteroaryl, heterocycloalkyl, R⁴, —C(═O)—R⁴,—C(═O)—NY¹Y², —NY¹Y² and —OR⁴. R¹ more preferably represents optionallysubstituted indolyl, optionally substituted indolizinyl or optionallysubstituted pyrrolyl and is more especially optionally substitutedindol-3-yl, indolizin-1-yl or optionally substituted pyrrol-3-yl.

[0087] R¹ may also particularly represent optionally substituted aryl,especially optionally substituted phenyl. Optional substituents includeone or more groups selected from alkylenedioxy, halo, R⁴, —NY¹Y² and—OR⁴. R¹ still more preferably represents 4-substituted phenyl, moreespecially 4-tertiarybutylphenyl,

[0088] R² may particularly represent hydrogen.

[0089] R² may also particularly represent halo.

[0090] R² may also particularly represent lower alkyl optionallysubstituted by carboxy, cyano, halo, hydroxy, tetrazolyl, or —CONY³Y⁴.

[0091] R² may also particularly represent lower alkenyl.

[0092] R³ may particularly represent hydrogen.

[0093] R³ may also particularly represent optionally substituted aryl,especially optionally substituted phenyl.

[0094] R³ may also particularly represent lower alkyl (e.g. methyl).

[0095] X¹ may particularly represent N.

[0096] X¹ may also particularly represent CH.

[0097] X¹ may also particularly represent C-lower alkoxy, especiallyC—OCH₃.

[0098] X¹ may also particularly represent C-aryl, especially C-phenyl.

[0099] X¹ may also particularly represent C-halo, especially C—Cl.

[0100] X¹ may also particularly represent C—CN.

[0101] It is to be understood that this invention covers all appropriatecombinations of the particular and preferred groupings referred toherein.

[0102] A particular preferred group of compounds of the invention arecompounds of formula (Ia):

[0103] in which R², R³ and X¹ are as hereinbefore defined; R⁹ ishydrogen, R⁴, alkenyl or heterocycloalkyl; R¹⁰ is alkenyloxy, carboxy(or an acid bioisostere), cyano, halo, hydroxy, heteroaryl, R⁴,—C(═O)—R⁴, —C(═O)—NY¹Y², —OR⁴, —N(R⁶)—C(═O)—R⁷, —N(R⁶)—SO₂—R⁷ or —NY¹Y²;and p is zero, or an integer 1 or 2; and their prodrugs andpharmaceutically acceptable salts, and solvates (e.g. hydrates) ofcompounds of formula (Ia) and their prodrugs.

[0104] Compounds of formula (Ia) in which R² represents hydrogen arepreferred.

[0105] Compounds of formula (Ia) in which R³ is hydrogen, optionallysubstituted aryl (e.g. phenyl) or lower alkyl (e.g. methyl), especiallyhydrogen, are preferred.

[0106] Compounds of formula (Ia) in which X¹ is CH, C-lower alkoxy (e.g.C—OCH₃), C-aryl, (e.g. C-phenyl), C-halo (e.g. C—Cl), C—CN or N arepreferred.

[0107] Compounds of formula (Ia) in which R⁹ represents:

[0108] (i) hydrogen;

[0109] (ii) C₁₋₄alkyl [e.g. —CH₃];

[0110] (iii) C₁₋₄alkyl substituted by hydroxy [e.g. —CH₂OH, —CH₂CH₂OH or—CH₂CH₂CH₂OH];

[0111] (iv) C₁₋₄alkyl substituted by —N(R⁶)C(═O)—R⁷ [e.g.—CH₂CH₂CH₂NHC(═O)CH₃];

[0112] (v) C₁₋₄alkyl substituted by —C(═O)—NY¹Y² [e.g.

[0113] (vi) cycloalkylalkyl substituted by hydroxy

[0114] are preferred. Compounds of formula (Ia) in which R⁹ representshydrogen or —CH₃ are especially preferred.

[0115] Compounds of formula (Ia) in which R¹⁰ represents:

[0116] (i) hydroxy;

[0117] (ii) —OR⁴ in which R⁴ is alkyl [e.g. —OCH₃];

[0118] (iii) —OR⁴ in which R⁴ is alkyl or cycloalkylalkyl substituted byone or more hydroxy groups [e.g. —OCH₂CH₂OH, —OCH₂CH₂CH₂OH,—OCH(CH₃)CH₂OH,

[0119] (iv) —OR⁴ in which R⁴ is alkyl substituted by one or more alkoxygroups [e.g. —OCH(CH₃)CH₂OCH₃];

[0120] (v) —OR⁴ in which R⁴ is alkyl or cycloalkyl substituted by one ormore carboxy groups

[0121] (vi) —OR⁴ in which R⁴ is cycloalkyl substituted by

[0122] (vii) —N(R⁶)—C(═O)—R⁷ [e.g. —NHC(═O)CH₃];

[0123] (viii) —CONY¹Y² [e.g. —CONH₂, —CONHCH₃, —CONHCH(CH₂OH)₂,—CONHCH₂CH₂OH, —CONHC(CH₃)₂CH₂OH, —CONHCH₂CH₂OCH₃, —CONHCH₂CH₂CO₂H,CONHCH₂CH₂CONH₂ or

[0124] (ix) carboxy

[0125] (x) alkyl substituted by carboxy [e.g. —CH₂CH₂CO₂H];

[0126] (xi) heteroaryl

[0127] (xii) —C(═O)—R⁴ in which R⁴ is alkyl [e.g. —C(═O)—CH₃]; or

[0128] are preferred. Compounds of formula (Ia) in which R¹⁰ represents

[0129] are especially preferred.

[0130] When p is 1, R¹⁰ is preferably attached to position 5 of theindolyl ring.

[0131] When p is 2, the R¹⁰ groups are preferably attached to positions5 and 6 of the indolyl ring.

[0132] A preferred group of compounds of the invention are compounds offormula (Ia) in which: R² is hydrogen; R³ is hydrogen, optionallysubstituted aryl (e.g. phenyl) or lower alkyl (e.g. methyl), especiallyhydrogen; X¹ is CH, C-lower alkoxy [especially C—OCH₃], C-aryl[especially C-phenyl], C-halo [especially C—Cl] or C—CN; R⁹ is (i)hydrogen, (ii) C₁₋₄alkyl [e.g. —CH₃], (iii) C₁₋₄alkyl substituted byhydroxy [e.g. —CH₂OH, —CH₂CH₂OH or —CH₂CH₂CH₂OH], (iv) C₁₋₄alkylsubstituted by —N(R⁶)C(═O)—R⁷ [e.g. —CH₂CH₂CH₂NHC(═O)CH₃], (v) C₁₋₄alkylsubstituted by

[0133] or (vi) cycloalkylalkyl substituted by hydroxy

[0134] R¹⁰ is (i) hydroxy, (ii) —OR⁴ in which R⁴ is alkyl [e.g. —OCH₃],(iii) —OR⁴ in which R⁴ is alkyl or cycloalkylalkyl substituted by one ormore hydroxy groups [e.g. —OCH₂CH₂OH, —OCH₂CH₂CH₂OH, —OCH₂CH (OH)CH₂OH,—OCH₂CH(OH)CH₃,

[0135] in which R⁴ is alkyl substituted by one or more alkoxy groups[e.g. —OCH(CH₃)CH₂OCH₃], (v) —OR⁴ in which R⁴ is alkyl or cycloalkylsubstituted by one or more carboxy groups [e.g. —OCH₂CO₂H, —OCH(CH₃)CO₂Hor

[0136] in which R⁴ is cycloalkyl substituted by —C(═O)—NY¹Y² [e.g.

[0137] (vii) —N(R⁶)—C(═O)—R⁷ [e.g. —NHC(═O)CH₃]; (viii) —CONY¹Y² [e.g.—CONH₂, —CONHCH₃, —CONHCH(CH₂OH)₂, —CONHCH₂CH₂OH, —CONHC(CH₃)₂CH₂OH,—CONHCH₂CH₂OCH₃, —CONHCH₂CH₂CO₂H,

[0138] (ix) carboxy, (x) alkyl substituted by carboxy

[0139] or pyridyl], (xii) —C(═O)—R⁴ in which R⁴ is alkyl [e.g.—C(═O)—CH₃] or (xii) tetrazolyl or N-methyltetrazolyl; the R¹⁰ group isattached to position 5 of the indolyl ring when p is 1 and the R¹⁰groups are attached to position 5 and 6 of the indolyl ring when p is 2;and the corresponding N-oxides, and their prodrugs; and pharmaceuticallyacceptable salts and solvates (e.g. hydrates) of such compounds andtheir N-oxides and prodrugs.

[0140] A further preferred group of compounds of the invention arecompounds of formula (Ia) in which: R² is hydrogen; R³ is hydrogen orlower alkyl (e.g. methyl), especially hydrogen; X¹ is N; R⁹ is (i)hydrogen, (ii) C₁₋₄alkyl [e.g. —CH₃], (iii) C₁₋₄alkyl substituted byhydroxy [e.g. —CH₂OH, —CH₂CH₂OH or —CH₂CH₂CH₂OH], (iv) C₁₋₄alkylsubstituted by —N(R⁶)C(═O)—R⁷ [e.g. —CH₂CH₂CH₂NHC(═O)CH₃], (v) C₁₋₄alkylsubstituted by

[0141] or (vi) cycloalkylalkyl substituted by hydroxy

[0142] R¹⁰ is (i) hydroxy, (ii) —OR⁴ in which R⁴ is alkyl [e.g. —OCH₃](iii) —OR⁴ in which R⁴ is alkyl or cycloalkylalkyl substituted by one ormore hydroxy groups [e.g. —OCH₂CH₂OH, —OCH₂CH₂CH₂OH, —OCH₂CH(OH)CH₂OH,—OCH₂CH(OH)CH₃,

[0143] (iv) —OR⁴ in which R⁴ is alkyl substituted by one or more alkoxygroups [e.g. —OCH(CH₃)CH₂OCH₃], (v) —OR⁴ in which R⁴ is alkyl orcycloalkyl substituted by one or more carboxy groups [e.g. —OCH₂CO₂H,—OCH(CH₃)CO₂H or

[0144] (vi) —OR⁴ in which R⁴ is cycloalkyl substituted by —C(═O)—NY¹Y²[e.g.

[0145] (vii) —N(R⁶)—C(═O)—R⁷ [e.g. —NHC(═O)CH₃]; (viii) —CONY¹Y² [e.g.—CONH₂, —CONHCH₃,—CONHCH(CH₂OH)₂, —CONHCH₂CH₂OH, —CONHC(CH₃)₂CH₂OH,—CONHCH₂CH₂OCH₃, —CONHCH₂CH₂CO₂H,

[0146] (ix) carboxy, (x) alkyl substituted by carboxy [e.g.—CH₂CH₂CO₂H], (xi) heteroaryl

[0147] or pyridyl], (xii) —C(═O)—R⁴ in which R⁴ is alkyl [e.g.—C(═O)—CH₃] or (xii) tetrazolyl or N-methyltetrazolyl; the R¹⁰ group isattached to position 5 of the indolyl ring when p is 1 and the R¹⁰groups are attached to position 5 and 6 of the indolyl ring when p is 2;and the corresponding N-oxides, and their prodrugs; and pharmaceuticallyacceptable salts and solvates (e.g. hydrates) of such compounds andtheir N-oxides and prodrugs.

[0148] Another particular group of compounds of the invention arecompounds of formula (Ib):

[0149] in which R², R³, R⁹, R¹⁰, X¹ and p are as hereinbefore defined,and their prodrugs and pharmaceutically acceptable salts, and solvates(e.g. hydrates) of compounds of formula (Ib) and their prodrugs.

[0150] Compounds of formula (Ib) in which R² represents hydrogen arepreferred.

[0151] Compounds of formula (Ib) in which R³ is hydrogen, optionallysubstituted aryl (e.g. phenyl) or lower alkyl (e.g. methyl), especiallyhydrogen, are preferred.

[0152] Compounds of formula (Ib) in which X¹ is CH, C-lower alkoxy (e.g.C—OCH₃), C-aryl, (e.g. C-phenyl), C-halo (e.g. C—Cl), C—CN or N arepreferred.

[0153] Compounds of formula (Ib) in which R⁹ represents hydrogen arepreferred.

[0154] Compounds of formula (Ib) in which R⁹ represents C₁₋₄alkyl [e.g.—CH₃] are also preferred.

[0155] Compounds of formula (Ib) in which p is zero are preferred.

[0156] A preferred group of compounds of the invention are compounds offormula (Ib) in which: R² is hydrogen; R³ is hydrogen, optionallysubstituted aryl (e.g. phenyl) or lower alkyl (e.g. methyl), especiallyhydrogen; X¹ is CH, C-lower alkoxy [especially C—OCH₃], C-aryl[especially C-phenyl], C-halo [especially C—Cl] or C—CN; R⁹ is hydrogenor C₁₋₄alkyl [e.g. —CH₃]; p is zero; and the corresponding N-oxides, andtheir prodrugs; and pharmaceutically acceptable salts and solvates (e.g.hydrates) of such compounds and their N-oxides and prodrugs.

[0157] A further preferred group of compounds of the invention arecompounds of formula (Ib) in which: R² is hydrogen; R³ is hydrogen orlower alkyl (e.g. methyl), especially hydrogen; X¹ is N; R⁹ is hydrogenor C₁₋₄alkyl [e.g. —CH₃]; p is zero; and the corresponding N-oxides, andtheir prodrugs; and pharmaceutically acceptable salts and solvates (e.g.hydrates) of such compounds and their N-oxides and prodrugs.

[0158] Another particular group of compounds of the invention arecompounds of formula (Ic):

[0159] in which R², R³, R⁹, R¹⁰, X¹ and p are as hereinbefore defined,and their prodrugs and pharmaceutically acceptable salts, and solvates(e.g. hydrates) of compounds of formula (Ic) and their prodrugs.

[0160] Compounds of formula (Ic) in which R² represents hydrogen arepreferred.

[0161] Compounds of formula (Ic) in which R³ is hydrogen, optionallysubstituted aryl (e.g. phenyl) or lower alkyl (e.g. methyl), especiallyhydrogen, are preferred.

[0162] Compounds of formula (Ic) in which X¹ is CH, C-lower alkoxy (e.g.C—OCH₃), C-aryl, (e.g. C-phenyl), C-halo (e.g. C—Cl), C—CN or N arepreferred.

[0163] Compounds of formula (Ic) in which R⁹ represents C₁₋₄alkyl [e.g.—CH₃] are also preferred.

[0164] Compounds of formula (Ic) in which p is 1 are preferred.

[0165] Compounds of formula (Ic) in which R¹⁰ represents aryl [e.g.phenyl] are preferred.

[0166] R¹⁰ is preferably attached at position 4 of the pyrrole ring.

[0167] A preferred group of compounds of the invention are compounds offormula (Ic) in which: R² is hydrogen; R³ is hydrogen, optionallysubstituted aryl (e.g. phenyl) or lower alkyl (e.g. methyl), especiallyhydrogen; X¹ is CH, C-lower alkoxy [especially C—OCH₃], C-aryl[especially C-phenyl], C-halo [especially C—Cl] or C—CN; R⁹ is C₁₋₄alkyl[e.g. —CH₃]; p is 1; R¹⁰ is aryl [e.g. phenyl] and R¹⁰ is attached atposition 4 of the pyrrole ring; and the corresponding N-oxides, andtheir prodrugs; and pharmaceutically acceptable salts and solvates (e.g.hydrates) of such compounds and their N-oxides and prodrugs. R³ ishydrogen, optionally substituted aryl (e.g. phenyl) or lower alkyl (e.g.methyl), especially hydrogen; X¹ is CH, C-lower alkoxy [especiallyC—OCH₃], C-aryl [especially C-phenyl], C-halo [especially C—Cl] or C—CN;

[0168] A further preferred group of compounds of the invention arecompounds of formula (Ic) in which: R² is hydrogen; R³ is hydrogen; X¹is N; R⁹ is C₁₋₄alkyl [e.g. —CH₃]; p is 1; R¹⁰ is aryl [e.g. phenyl] andR¹⁰ is attached at position 4 of the pyrrole ring; and the correspondingN-oxides, and their prodrugs; and pharmaceutically acceptable salts andsolvates (e.g. hydrates) of such compounds and their N-oxides andprodrugs.

[0169] Another particular group of compounds of the invention arecompounds of formula (Id):

[0170] in which R², R³, R¹⁰, X¹ and p are as hereinbefore defined, andtheir prodrugs and pharmaceutically acceptable salts, and solvates (e.g.hydrates) of compounds of formula (Id) and their prodrugs.

[0171] Compounds of formula (Id) in which R² represents hydrogen, loweralkyl (e.g. methyl), lower alkyl substituted by —CONY³Y⁴ (e.g.—CH₂CH₂CONH₂ or —CH₂CH₂CONHCH₃), lower alkyl substituted by carboxy(e.g. —CH₂CH₂CO₂H), lower alkyl substituted by tetrazolyl (e.g.

[0172] or lower alkyl substituted by hydroxy [e.g. —CH₂CH₂CH₂OH] arepreferred.

[0173] Compounds of formula (Id) in which R³ is hydrogen, optionallysubstituted aryl (e.g. phenyl) or lower alkyl (e.g. methyl), especiallyhydrogen, are preferred.

[0174] Compounds of formula (Id) in which X¹ is CH, C-lower alkoxy (e.g.C—OCH₃), C-aryl, (e.g. C-phenyl), C-halo (e.g. C—Cl), C—CN or N arepreferred.

[0175] Compounds of formula (Id) in which p is 1 are preferred.

[0176] Compounds of formula (Id) in which R¹⁰ represents alkyl [e.g.tertiarybutyl] are preferred.

[0177] R¹⁰ is preferably attached at position 4.

[0178] A preferred group of compounds of the invention are compounds offormula (Id) in which: R² is hydrogen, lower alkyl (e.g. methyl), loweralkyl substituted by —CONY³Y⁴ (e.g. —CH₂CH₂CONH₂ or —CH₂CH₂CONHCH₃),lower alkyl substituted by carboxy (e.g. —CH₂CH₂CO₂H), lower alkylsubstituted by tetrazolyl

[0179] or lower alkyl substituted by hydroxy [e.g. —CH₂CH₂CH₂OH]; R³ ishydrogen, optionally substituted aryl (e.g. phenyl) or lower alkyl (e.g.methyl), especially hydrogen; X¹ is CH, C-lower alkoxy [especiallyC—OCH₃], C-aryl [especially C-phenyl], C-halo [especially C—Cl] or C—CN;p is 1; R¹⁰ is alkyl [e.g. tertiary-butyl] and R¹⁰ is attached atposition 4; and the corresponding N-oxides, and their prodrugs; andpharmaceutically acceptable salts and solvates (e.g. hydrates) of suchcompounds and their N-oxides and prodrugs.

[0180] A further preferred group of compounds of the invention arecompounds of formula (Id) in which: R² is hydrogen, lower alkyl (e.g.methyl), lower alkyl substituted by —CONY³Y⁴ (e.g. —CH₂CH₂CONH₂ or—CH₂CH₂CONHCH₃), lower alkyl substituted by carboxy (e.g. —CH₂CH₂CO₂H),lower alkyl substituted by tetrazolyl

[0181] or lower alkyl substituted by hydroxy [e.g. —CH₂CH₂CH₂OH]; R³ ishydrogen; X¹ is N; p is 1; R¹⁰ is alkyl [e.g. tertiary-butyl] and R¹⁰ isattached at position 4; and the corresponding N-oxides, and theirprodrugs; and pharmaceutically acceptable salts and solvates (e.g.hydrates) of such compounds and their N-oxides and prodrugs.

[0182] Particular compounds of the invention of formula (Ia) areselected from the compounds formed by joining the carbon atom (C*) ofone of the azaindoles fragments (A1 to A28) shown in Table 1 to thecarbon atom (*C) in the five membered ring of one of the fragments (B1to B19) shown in Table 2, and joining the carbon atom (C*) of the phenylring in one of the fragments (B1 to B19) shown in Table 2 to the oxygenatom (*O) of one of the fragments (C1 to C19) depicted in Table 3.

[0183] Particular compounds of the invention of formula (Ia) are alsoselected from the compounds formed by joining the carbon atom (C*) ofone of the azaindoles fragments (A1 to A28) shown in Table 1 to thecarbon atom (*C) in the five membered ring of one of the fragments (B1to B19) shown in Table 2, and joining the carbon atom (C*) of the phenylring in one of the fragments (B1 to B19) shown in Table 2 to the carbonatom (*C) of one of the fragments (C20 to C44) depicted in Table 3.

[0184] Particular compounds of the invention of formula (Ia) are alsoselected from the compounds formed by joining the carbon atom (C*) ofone of the azaindoles fragments (A1 to A28) shown in Table 1 to thecarbon atom (*C) in the five membered ring of one of the fragments (B1to B19) shown in Table 2, and joining the carbon atom (C*) of the phenylring in one of the fragments (B1 to B19) shown in Table 2 to thenitrogen atom (*N) of the fragment (C45) or a hydrogen atom (*H,fragment (C46)) depicted in Table 3.

[0185] Particular compounds of the invention of formula (Ib) areselected from the compounds formed by joining the carbon atom (C*) ofone of the azaindoles fragments (A1 to A28) shown in Table 1 to thecarbon atom (*C) in the five membered ring of one of the indolizinefragments (B20 or B21) shown in Table 2, and joining the carbon atom(C*) in the six membered ring of one of the indolizine fragments (B20 orB21) shown in Table 2 to (i) the oxygen atom (*O) of one of thefragments (C1 to C19), (ii) the carbon atom (*C) of one of the fragments(C20 to C42), (iii) the nitrogen atom (*N) of the fragment (C45) or (iv)a hydrogen atom (*H, fragment (C46)) depicted in Table 3.

[0186] Particular compounds of the invention of formula (Ib) are alsoselected from the compounds formed by joining the carbon atom (C*) ofone of the azaindoles fragments (A1 to A28) shown in Table 1 to thecarbon atom (*C) in the indolizine fragments (B22) shown in Table 2.

[0187] Particular compounds of the invention of formula (Ic) areselected from the compounds formed by joining the carbon atom (C*) ofone of the azaindoles fragments (A1 to A28) shown in Table 1 to thecarbon atom (*C) in one of the pyrrole fragments (B23 to B32) shown inTable 2.

[0188] Particular compounds of the invention of formula (Id) areselected from the compounds formed by joining the carbon atom (C*) ofone of the azaindoles fragments (A29 to A41) shown in Table 1 to thecarbon atom (*C) in one of the fragments (B33 to B44) shown in Table 2.TABLE 1 A1

A2

A3

A4

A5

A6

A7

A8

A9

A10

A11

A12

A13

A14

A15

A16

A17

A18

A19

A20

A21

A22

A23

A24

A25

A26

A27

A28

A29

A30

A31

A32

A33

A34

A35

A36

A37

A38

A39

A40

A41

[0189] TABLE 2 B1

B2

B3

B4

B5

B6

B7

B8

B9

B10

B11

B12

B13

B14

B15

B16

B17

B18

B19

B20

B21

B22

B23

B24

B25

B26

B27

B28

B29

B30

B31

B32

B33

B34

B35

B36

B37

B38

B38

B40

B41

B42

B43

B44

[0190] TABLE 3 C1 *O—CH₃ C2

C3

C4

C5

C6

C7

C8

C9

C10 *O—H C11

C12

C13

C14

C15

C16

C17

C18

C19

C20

C21 *CH₂—CH₂—CO₂H C22 *CH₂—CH₂—CONH₂ C23

C24

C25

C26

C27

C28

C29

C30

C31

C32

C33

C34

C35

C36

C37

C38

C39

C40

C41 *CH₂—NH—SO₂—CH₃ C42

C43

C44 *CH₂—NH—CO—NHCH₂CH₃ C45

C46 *H

[0191] A1-B1-C1; A1-B1-C2; A1-B1-C3; A1-B1-C4; A1-B1-C5; A1-B1-C6;A1-B1-C7; A1-B1-C8; A1-B1-C9; A1-B1-C10; A1-B1-C11; A1-B1-C12;A1-B1-C13; A1-B1-C14; A1-B1-C15; A1-B1-C16; A1-B1-C17; A1-B1-C18;A1-B1-C19; A1-B1-C20; A1-B1-C21; A1-B1-C22; A1-B1-C23; A1-B1-C24;A1-B1-C25; A1-B1-C26; A1-B1-C27; A1-B1-C28; A1-B1-C29; A1-B1-C30;A1-B1-C31; A1-B1-C32; A1-B1-C33; A1-B1-C34; A1-B1-C35; A1-B1-C36;A1-B1-C37; A1-B1-C38; A1-B1-C39; A1-B1-C40; A1-B1-C41; A1-B1-C42;A1-B1-C43; A1-B1-C44; A1-B1-C45; A1-B1-C46; A2-B1-C1; A2-B1-C2;A2-B1-C3; A2-B1-C4; A2-B1-C5; A2-B1-C6; A2-B1-C7; A2-B1-C8; A2-B1-C9;A2-B1-C10; A2-B1-C11; A2-B1-C12; A2-B1-C13; A2-B1-C14; A2-B1-C15;A2-B1-C16; A2-B1-C17; A2-B1-C18; A2-B1-C19; A2-B1-C20; A2-B1-C21;A2-B1-C22; A2-B1-C23; A2-B1-C24; A2-B1-C25; A2-B1-C26; A2-B1-C27;A2-B1-C28; A2-B1-C29; A2-B1-C30; A2-B1-C31; A2-B1-C32; A2-B1-C33;A2-B1-C34; A2-B1-C35; A2-B1-C36; A2-B1-C37; A2-B1-C38; A2-B1-C39;A2-B1-C40; A2-B1-C41; A2-B1-C42; A2-B1-C43; A2-B1-C44; A2-B1-C45;A2-B1-C46; A3-B1-C1; A3-B1-C2; A3-B1-C3; A3-B1-C4; A3-B1-C5; A3-B1-C6;A3-B1-C7; A3-B1-C8; A3-B1-C9; A3-B1-C10; A3-B1-C11; A3-B1-C12;A3-B1-C13; A3-B1-C14; A3-B1-C15; A3-B1-C16; A3-B1-C17; A3-B1-C18;A3-B1-C19; A3-B1-C20; A3-B1-C21; A3-B1-C22; A3-B1-C23; A3-B1-C24;A3-B1-C25; A3-B1-C26; A3-B1-C27; A3-B1-C28; A3-B1-C29; A3-B1-C30;A3-B1-C31; A3-B1-C32; A3-B1-C33; A3-B1-C34; A3-B1-C35; A3-B1-C36;A3-B1-C37; A3-B1-C38; A3-B1-C39; A3-B1-C40; A3-B1-C41; A3-B1-C42;A3-B1-C43; A3-B1-C44; A3-B1-C45; A3-B1-C46; A4-B1-C1; A4-B1-C2;A4-B1-C3; A4-B1-C4; A4-B1-C5; A4-B1-C6; A4-B1-C7; A4-B1-C8; A4-B1-C9;A4-B1-C10; A4-B1-C11; A4-B1-C12; A4-B1-C13; A4-B1-C14; A4-B1-C15;A4-B1-C16; A4-B1-C17; A4-B1-C18; A4-B1-C19; A4-B1-C20; A4-B1-C21;A4-B1-C22; A4-B1-C23; A4-B1-C24; A4-B1-C25; A4-B1-C26; A4-B1-C27;A4-B1-C28; A4-B1-C29; A4-B1-C30; A4-B1-C31; A4-B1-C32; A4-B1-C33;A4-B1-C34; A4-B1-C35; A4-B1-C36; A4-B1-C37; A4-B1-C38; A4-B1-C39;A4-B1-C40; A4-B1-C41; A4-B1-C42; A4-B1-C43; A4-B1-C44; A4-B1-C45;A4-B1-C46; A5-B1-C1; A5-B1-C2; A5-B1-C3; A5-B1-C4; A5-B1-C5; A5-B1-C6;A5-B1-C7; A5-B1-C8; A5-B1-C9; A5-B1-C10; A5-B1-C11; A5-B1-C12;A5-B1-C13; A5-B1-C14; A5-B1-C15; A5-B1-C16; A5-B1-C17; A5-B1-C18;A5-B1-C19; A5-B1-C20; A5-B1-C21; A5-B1-C22; A5-B1-C23; A5-B1-C24;A5-B1-C25; A5-B1-C26; A5-B1-C27; A5-B1-C28; A5-B1-C29; A5-B1-C30;A5-B1-C31; A5-B1-C32; A5-B1-C33; A5-B1-C34; A5-B1-C35; A5-B1-C36;A5-B1-C37; A5-B1-C38; A5-B1-C39; A5-B1-C40; A5-B1-C41; A5-B1-C42;A5-B1-C43; A5-B1-C44; A5-B1-C45; A5-B1-C46; A6-B1-C1; A6-B1-C2;A6-B1-C3; A6-B1-C4; A6-B1-C5; A6-B1-C6; A6-B1-C7; A6-B1-C8; A6-B1-C9;A6-B1-C10; A6-B1-C11; A6-B1-C12; A6-B1-C13; A6-B1-C14; A6-B1-C15;A6-B1-C16; A6-B1-C17; A6-B1-C18; A6-B1-C19; A6-B1-C20; A6-B1-C21;A6-B1-C22; A6-B1-C23; A6-B1-C24; A6-B1-C25; A6-B1-C26; A6-B1-C27;A6-B1-C28; A6-B1-C29; A6-B1-C30; A6-B1-C31; A6-B1-C32; A6-B1-C33;A6-B1-C34; A6-B1-C35; A6-B1-C36; A6-B1-C37; A6-B1-C38; A6-B1-C39;A6-B1-C40; A6-B1-C41; A6-B1-C42; A6-B1-C43; A6-B1-C44; A6-B1-C45;A6-B1-C46; A7-B1-C1; A7-B1-C2; A7-B1-C3; A7-B1-C4; A7-B1-C5; A7-B1-C6;A7-B1-C7; A7-B1-C8; A7-B1-C9; A7-B1-C10; A7-B1-C11; A7-B1-C12;A7-B1-C13; A7-B1-C14; A7-B1-C15; A7-B1-C16; A7-B1-C17; A7-B1-C18;A7-B1-C19; A7-B1-C20; A7-B1-C21; A7-B1-C22; A7-B1-C23; A7-B1-C24;A7-B1-C25; A7-B1-C26; A7-B1-C27; A7-B1-C28; A7-B1-C29; A7-B1-C30;A7-B1-C31; A7-B1-C32; A7-B1-C33; A7-B1-C34; A7-B1-C35; A7-B1-C36;A7-B1-C37; A7-B1-C38; A7-B1-C39; A7-B1-C40; A7-B1-C41; A7-B1-C42;A7-B1-C43; A7-B1-C44; A7-B1-C45; A7-B1-C46; A8-B1-C1; A8-B1-C2;A8-B1-C3; A8-B1-C4; A8-B1-C5; A8-B1-C6; A8-B1-C7; A8-B1-C8; A8-B1-C9;A8-B1-C10; A8-B1-C11; A8-B1-C12; A8-B1-C13; A8-B1-C14; A8-B1-C15;A8-B1-C16; A8-B1-C17; A8-B1-C18; A8-B1-C19; A8-B1-C20; A8-B1-C21;A8-B1-C22; A8-B1-C23; A8-B1-C24; A8-B1-C25; A8-B1-C26; A8-B1-C27;A8-B1-C28; A8-B1-C29; A8-B1-C30; A8-B1-C31; A8-B1-C32; A8-B1-C33;A8-B1-C34; A8-B1-C35; A8-B1-C36; A8-B1-C37; A8-B1-C38; A8-B1-C39;A8-B1-C40; A8-B1-C41; A8-B1-C42; A8-B1-C43; A8-B1-C44; A8-B1-C45;A8-B1-C46; A9-B1-C1; A9-B1-C2; A9-B1-C3; A9-B1-C4; A9-B1-C5; A9-B1-C6;A9-B1-C7; A9-B1-C8; A9-B1-C9; A9-B1-C10; A9-B1-C11; A9-B1-C12;A9-B1-C13; A9-B1-C14; A9-B1-C15; A9-B1-C16; A9-B1-C17; A9-B1-C18;A9-B1-C19; A9-B1-C20; A9-B1-C21; A9-B1-C22; A9-B1-C23; A9-B1-C24;A9-B1-C25; A9-B1-C26; A9-B1-C27; A9-B1-C28; A9-B1-C29; A9-B1-C30;A9-B1-C31; A9-B1-C32; A9-B1-C33; A9-B1-C34; A9-B1-C35; A9-B1-C36;A9-B1-C37; A9-B1-C38; A9-B1-C39; A9-B1-C40; A9-B1-C41; A9-B1-C42;A9-B1-C43; A9-B1-C44; A9-B1-C45; A9-B1-C46; A10-B1-C1; A10-B1-C2;A10-B1-C3; A10-B1-C4; A10-B1-C5; A10-B1-C6; A10-B1-C7; A10-B1-C8;A10-B1-C9; A10-B1-C10; A10-B1-C11; A10-B1-C12; A10-B1-C13; A10-B1-C14;A10-B1-C15; A10-B1-C16; A10-B1-C17; A10-B1-C18; A10-B1-C19; A10-B1-C20;A10-B1-C21; A10-B1-C22; A10-B1-C23; A10-B1-C24; A10-B1-C25; A10-B1-C26;A10-B1-C27; A10-B1-C28; A10-B1-C29; A10-B1-C30; A10-B1-C31; A10-B1-C32;A10-B1-C33; A10-B1-C34; A10-B1-C35; A10-B1-C36; A10-B1-C37; A10-B1-C38;A10-B1-C39; A10-B1-C40; A10-B1-C41; A10-B1-C42; A10-B1-C43; A10-B1-C44;A10-B1-C45; A10-B1-C46; A11-B1-C1; A11-B1-C2; A11-B1-C3; A11-B1-C4;A11-B1-C5; A11-B1-C6; A11-B1-C7; A11-B1-C8; A11-B1-C9; A11-B1-C10;A11-B1-C11; A11-B1-C12; A11-B1-C13; A11-B1-C14; A11-B1-C15; A11-B1-C16;A11-B1-C17; A11-B1-C18; A11-B1-C19; A11-B1-C20; A11-B1-C21; A11-B1-C22;A11-B1-C23; A11-B1-C24; A11-B1-C25; A11-B1-C26; A11-B1-C27; A11-B1-C28;A11-B1-C29; A11-B1-C30; A11-B1-C31; A11-B1-C32; A11-B1-C33; A11-B1-C34;A11-B1-C35; A11-B1-C36; A11-B1-C37; A11-B1-C38; A11-B1-C39; A11-B1-C40;A11-B1-C41; A11-B1-C42; A11-B1-C43; A11-B1-C44; A11-B1-C45; A11-B1-C46;A12-B1-C1; A12-B1-C2; A12-B1-C3; A12-B1-C4; A12-B1-C5; A12-B1-C6;A12-B1-C7; A12-B1-C8; A12-B1-C9; A12-B1-C10; A12-B1-C11; A12-B1-C12;A12-B1-C13; A12-B1-C14; A12-B1-C15; A12-B1-C16; A12-B1-C17; A12-B1-C18;A12-B1-C19; A12-B1-C20; A12-B1-C21; A12-B1-C22; A12-B1-C23; A12-B1-C24;A12-B1-C25; A12-B1-C26; A12-B1-C27; A12-B1-C28; A12-B1-C29; A12-B1-C30;A12-B1-C31; A12-B1-C32; A12-B1-C33; A12-B1-C34; A12-B1-C35; A12-B1-C36;A12-B1-C37; A12-B1-C38; A12-B1-C39; A12-B1-C40; A12-B1-C41; A12-B1-C42;A12-B1-C43; A12-B1-C44; A12-B1-C45; A12-B1-C46; A13-B1-C1; A13-B1-C2;A13-B1-C3; A13-B1-C4; A13-B1-C5; A13-B1-C6; A13-B1-C7; A13-B1-C8;A13-B1-C9; A13-B1-C10; A13-B1-C11; A13-B1-C12; A13-B1-C13; A13-B1-C14;A13-B1-C15; A13-B1-C16; A13-B1-C17; A13-B1-C18; A13-B1-C19; A13-B1-C20;A13-B1-C21; A13-B1-C22; A13-B1-C23; A13-B1-C24; A13-B1-C25; A13-B1-C26;A13-B1-C27; A13-B1-C28; A13-B1-C29; A13-B1-C30; A13-B1-C31; A13-B1-C32;A13-B1-C33; A13-B1-C34; A13-B1-C35; A13-B1-C36; A13-B1-C37; A13-B1-C38;A13-B1-C39; A13-B1-C40; A13-B1-C41; A13-B1-C42; A13-B1-C43; A13-B1-C44;A13-B1-C45; A13-B1-C46; A14-B1-C1; A14-B1-C2; A14-B1-C3; A14-B1-C4;A14-B1-C5; A14-B1-C6; A14-B1-C7; A14-B1-C8; A14-B1-C9; A14-B1-C10;A14-B1-C11; A14-B1-C12; A14-B1-C13; A14-B1-C14; A14-B1-C15; A14-B1-C16;A14-B1-C17; A14-B1-C18; A14-B1-C19; A14-B1-C20; A14-B1-C21; A14-B1-C22;A14-B1-C23; A14-B1-C24; A14-B1-C25; A14-B1-C26; A14-B1-C27; A14-B1-C28;A14-B1-C29; A14-B1-C30; A14-B1-C31; A14-B1-C32; A14-B1-C33; A14-B1-C34;A14-B1-C35; A14-B1-C36; A14-B1-C37; A14-B1-C38; A14-B1-C39; A14-B1-C40;A14-B1-C41; A14-B1-C42; A14-B1-C43; A14-B1-C44; A14-B1-C45; A14-B1-C46;A15-B1-C1; A15-B1-C2; A15-B1-C3; A15-B1-C4; A15-B1-C5; A15-B1-C6;A15-B1-C7; A15-B1-C8; A15-B1-C9; A15-B1-C10; A15-B1-C11; A15-B1-C12;A15-B1-C13; A15-B1-C14; A15-B1-C15; A15-B1-C16; A15-B1-C17; A15-B1-C18;A15-B1-C19; A15-B1-C20; A15-B1-C21; A15-B1-C22; A15-B1-C23; A15-B1-C24;A15-B1-C25; A15-B1-C26; A15-B1-C27; A15-B1-C28; A15-B1-C29; A15-B1-C30;A15-B1-C31; A15-B1-C32; A15-B1-C33; A15-B1-C34; A15-B1-C35; A15-B1-C36;A15-B1-C37; A15-B1-C38; A15-B1-C39; A15-B1-C40; A15-B1-C41; A15-B1-C42;A15-B1-C43; A15-B1-C44; A15-B1-C45; A15-B1-C46; A16-B1-C1; A16-B1-C2;A16-B1-C3; A16-B1-C4; A16-B1-C5; A16-B1-C6; A16-B1-C7; A16-B1-C8;A16-B1-C9; A16-B1-C10; A16-B1-C11; A16-B1-C12; A16-B1-C13; A16-B1-C14;A16-B1-C15; A16-B1-C16; A16-B1-C17; A16-B1-C18; A16-B1-C19; A16-B1-C20;A16-B1-C21; A16-B1-C22; A16-B1-C23; A16-B1-C24; A16-B1-C25; A16-B1-C26;A16-B1-C27; A16-B1-C28; A16-B1-C29; A16-B1-C30; A16-B1-C31; A16-B1-C32;A16-B1-C33; A16-B1-C34; A16-B1-C35; A16-B1-C36; A16-B1-C37; A16-B1-C38;A16-B1-C39; A16-B1-C40; A16-B1-C41; A16-B1-C42; A16-B1-C43; A16-B1-C44;A16-B1-C45; A16-B1-C46; A17-B1-C1; A17-B1-C2; A17-B1-C3; A17-B1-C4;A17-B1-C5; A17-B1-C6; A17-B1-C7; A17-B1-C8; A17-B1-C9; A17-B1-C10;A17-B1-C11; A17-B1-C12; A17-B1-C13; A17-B1-C14; A17-B1-C15; A17-B1-C16;A17-B1-C17; A17-B1-C18; A17-B1-C19; A17-B1-C20; A17-B1-C21; A17-B1-C22;A17-B1-C23; A17-B1-C24; A17-B1-C25; A17-B1-C26; A17-B1-C27; A17-B1-C28;A17-B1-C29; A17-B1-C30; A17-B1-C31; A17-B1-C32; A17-B1-C33; A17-B1-C34;A17-B1-C35; A17-B1-C36; A17-B1-C37; A17-B1-C38; A17-B1-C39; A17-B1-C40;A17-B1-C41; A17-B1-C42; A17-B1-C43; A17-B1-C44; A17-B1-C45; A17-B1-C46;A18-B1-C1; A18-B1-C2; A18-B1-C3; A18-B1-C4; A18-B1-C5; A18-B1-C6;A18-B1-C7; A18-B1-C8; A18-B1-C9; A18-B1-C10; A18-B1-C11; A18-B1-C12;A18-B1-C13; A18-B1-C14; A18-B1-C15; A18-B1-C16; A18-B1-C17; A18-B1-C18;A18-B1-C19; A18-B1-C20; A18-B1-C21; A18-B1-C22; A18-B1-C23; A18-B1-C24;A18-B1-C25; A18-B1-C26; A18-B1-C27; A18-B1-C28; A18-B1-C29; A18-B1-C30;A18-B1-C31; A18-B1-C32; A18-B1-C33; A18-B1-C34; A18-B1-C35; A18-B1-C36;A18-B1-C37; A18-B1-C38; A18-B1-C39; A18-B1-C40; A18-B1-C41; A18-B1-C42;A18-B1-C43; A18-B1-C44; A18-B1-C45; A18-B1-C46; A19-B1-C1; A19-B1-C2;A19-B1-C3; A19-B1-C4; A19-B1-C5; A19-B1-C6; A19-B1-C7; A19-B1-C8;A19-B1-C9; A19-B1-C10; A19-B1-C11; A19-B1-C12; A19-B1-C13; A19-B1-C14;A19-B1-C15; A19-B1-C16; A19-B1-C17; A19-B1-C18; A19-B1-C19; A19-B1-C20;A19-B1-C21; A19-B1-C22; A19-B1-C23; A19-B1-C24; A19-B1-C25; A19-B1-C26;A19-B1-C27; A19-B1-C28; A19-B1-C29; A19-B1-C30; A19-B1-C31; A19-B1-C32;A19-B1-C33; A19-B1-C34; A19-B1-C35; A19-B1-C36; A19-B1-C37; A19-B1-C38;A19-B1-C39; A19-B1-C40; A19-B1-C41; A19-B1-C42; A19-B1-C43; A19-B1-C44;A19-B1-C45; A19-B1-C46; A20-B1-C1; A20-B1-C2; A20-B1-C3; A20-B1-C4;A20-B1-C5; A20-B1-C6; A20-B1-C7; A20-B1-C8; A20-B1-C9; A20-B1-C10;A20-B1-C11; A20-B1-C12; A20-B1-C13; A20-B1-C14; A20-B1-C15; A20-B1-C16;A20-B1-C17; A20-B1-C18; A20-B1-C19; A20-B1-C20; A20-B1-C21; A20-B1-C22;A20-B1-C23; A20-B1-C24; A20-B1-C25; A20-B1-C26; A20-B1-C27; A20-B1-C28;A20-B1-C29; A20-B1-C30; A20-B1-C31; A20-B1-C32; A20-B1-C33; A20-B1-C34;A20-B1-C35; A20-B1-C36; A20-B1-C37; A20-B1-C38; A20-B1-C39; A20-B1-C40;A20-B1-C41; A20-B1-C42; A20-B1-C43; A20-B1-C44; A20-B1-C45; A20-B1-C46;A21-B1-C1; A21-B1-C2; A21-B1-C3; A21-B1-C4; A21-B1-C5; A21-B1-C6;A21-B1-C7; A21-B1-C8; A21-B1-C9; A21-B1-C10; A21-B1-C11; A21-B1-C12;A21-B1-C13; A21-B1-C14; A21-B1-C15; A21-B1-C16; A21-B1-C17; A21-B1-C18;A21-B1-C19; A21-B1-C20; A21-B1-C21; A21-B1-C22; A21-B1-C23; A21-B1-C24;A21-B1-C25; A21-B1-C26; A21-B1-C27; A21-B1-C28; A21-B1-C29; A21-B1-C30;A21-B1-C31; A21-B1-C32; A21-B1-C33; A21-B1-C34; A21-B1-C35; A21-B1-C36;A21-B1-C37; A21-B1-C38; A21-B1-C39; A21-B1-C40; A21-B1-C41; A21-B1-C42;A21-B1-C43; A21-B1-C44; A21-B1-C45; A21-B1-C46; A22-B1-C1; A22-B1-C2;A22-B1-C3; A22-B1-C4; A22-B1-C5; A22-B1-C6; A22-B1-C7; A22-B1-C8;A22-B1-C9; A22-B1-C10; A22-B1-C11; A22-B1-C12; A22-B1-C13; A22-B1-C14;A22-B1-C15; A22-B1-C16; A22-B1-C17; A22-B1-C18; A22-B1-C19; A22-B1-C20;A22-B1-C21; A22-B1-C22; A22-B1-C23; A22-B1-C24; A22-B1-C25; A22-B1-C26;A22-B1-C27; A22-B1-C28; A22-B1-C29; A22-B1-C30; A22-B1-C31; A22-B1-C32;A22-B1-C33; A22-B1-C34; A22-B1-C35; A22-B1-C36; A22-B1-C37; A22-B1-C38;A22-B1-C39; A22-B1-C40; A22-B1-C41; A22-B1-C42; A22-B1-C43; A22-B1-C44;A22-B1-C45; A22-B1-C46; A23-B1-C1; A23-B1-C2; A23-B1-C3; A23-B1-C4;A23-B1-C5; A23-B1-C6; A23-B1-C7; A23-B1-C8; A23-B1-C9; A23-B1-C10;A23-B1-C11; A23-B1-C12; A23-B1-C13; A23-B1-C14; A23-B1-C15; A23-B1-C16;A23-B1-C17; A23-B1-C18; A23-B1-C19; A23-B1-C20; A23-B1-C21; A23-B1-C22;A23-B1-C23; A23-B1-C24; A23-B1-C25; A23-B1-C26; A23-B1-C27; A23-B1-C28;A23-B1-C29; A23-B1-C30; A23-B1-C31; A23-B1-C32; A23-B1-C33; A23-B1-C34;A23-B1-C35; A23-B1-C36; A23-B1-C37; A23-B1-C38; A23-B1-C39; A23-B1-C40;A23-B1-C41; A23-B1-C42; A23-B1-C43; A23-B1-C44; A23-B1-C45; A23-B1-C46;A24-B1-C1; A24-B1-C2; A24-B1-C3; A24-B1-C4; A24-B1-C5; A24-B1-C6;A24-B1-C7; A24-B1-C8; A24-B1-C9; A24-B1-C10; A24-B1-C11; A24-B1-C12;A24-B1-C13; A24-B1-C14; A24-B1-C15; A24-B1-C16; A24-B1-C17; A24-B1-C18;A24-B1-C19; A24-B1-C20; A24-B1-C21; A24-B1-C22; A24-B1-C23; A24-B1-C24;A24-B1-C25; A24-B1-C26; A24-B1-C27; A24-B1-C28; A24-B1-C29; A24-B1-C30;A24-B1-C31; A24-B1-C32; A24-B1-C33; A24-B1-C34; A24-B1-C35; A24-B1-C36;A24-B1-C37; A24-B1-C38; A24-B1-C39; A24-B1-C40; A24-B1-C41; A24-B1-C42;A24-B1-C43; A24-B1-C44; A24-B1-C45; A24-B1-C46; A25-B1-C1; A25-B1-C2;A25-B1-C3; A25-B1-C4; A25-B1-C5; A25-B1-C6; A25-B1-C7; A25-B1-C8;A25-B1-C9; A25-B1-C10; A25-B1-C11; A25-B1-C12; A25-B1-C13; A25-B1-C14;A25-B1-C15; A25-B1-C16; A25-B1-C17; A25-B1-C18; A25-B1-C19; A25-B1-C20;A25-B1-C21; A25-B1-C22; A25-B1-C23; A25-B1-C24; A25-B1-C25; A25-B1-C26;A25-B1-C27; A25-B1-C28; A25-B1-C29; A25-B1-C30; A25-B1-C31; A25-B1-C32;A25-B1-C33; A25-B1-C34; A25-B1-C35; A25-B1-C36; A25-B1-C37; A25-B1-C38;A25-B1-C39; A25-B1-C40; A25-B1-C41; A25-B1-C42; A25-B1-C43; A25-B1-C44;A25-B1-C45; A25-B1-C46; A26-B1-C1; A26-B1-C2; A26-B1-C3; A26-B1-C4;A26-B1-C5; A26-B1-C6; A26-B1-C7; A26-B1-C8; A26-B1-C9; A26-B1-C10;A26-B1-C11; A26-B1-C12; A26-B1-C13; A26-B1-C14; A26-B1-C15; A26-B1-C16;A26-B1-C17; A26-B1-C18; A26-B1-C19; A26-B1-C20; A26-B1-C21; A26-B1-C22;A26-B1-C23; A26-B1-C24; A26-B1-C25; A26-B1-C26; A26-B1-C27; A26-B1-C28;A26-B1-C29; A26-B1-C30; A26-B1-C31; A26-B1-C32; A26-B1-C33; A26-B1-C34;A26-B1-C35; A26-B1-C36; A26-B1-C37; A26-B1-C38; A26-B1-C39; A26-B1-C40;A26-B1-C41; A26-B1-C42; A26-B1-C43; A26-B1-C44; A26-B1-C45; A26-B1-C46;A27-B1-C1; A27-B1-C2; A27-B1-C3; A27-B1-C4; A27-B1-C5; A27-B1-C6;A27-B1-C7; A27-B1-C8; A27-B1-C9; A27-B1-C10; A27-B1-C11; A27-B1-C12;A27-B1-C13; A27-B1-C14; A27-B1-C15; A27-B1-C16; A27-B1-C17; A27-B1-C18;A27-B1-C19; A27-B1-C20; A27-B1-C21; A27-B1-C22; A27-B1-C23; A27-B1-C24;A27-B1-C25; A27-B1-C26; A27-B1-C27; A27-B1-C28; A27-B1-C29; A27-B1-C30;A27-B1-C31; A27-B1-C32; A27-B1-C33; A27-B1-C34; A27-B1-C35; A27-B1-C36;A27-B1-C37; A27-B1-C38; A27-B1-C39; A27-B1-C40; A27-B1-C41; A27-B1-C42;A27-B1-C43; A27-B1-C44; A27-B1-C45; A27-B1-C46; A28-B1-C1; A28-B1-C2;A28-B1-C3; A28-B1-C4; A28-B1-C5; A28-B1-C6; A28-B1-C7; A28-B1-C8;A28-B1-C9; A28-B1-C10; A28-B1-C11; A28-B1-C12; A28-B1-C13; A28-B1-C14;A28-B1-C15; A28-B1-C16; A28-B1-C17; A28-B1-C18; A28-B1-C19; A28-B1-C20;A28-B1-C21; A28-B1-C22; A28-B1-C23; A28-B1-C24; A28-B1-C25; A28-B1-C26;A28-B1-C27; A28-B1-C28; A28-B1-C29; A28-B1-C30; A28-B1-C31; A28-B1-C32;A28-B1-C33; A28-B1-C34; A28-B1-C35; A28-B1-C36; A28-B1-C37; A28-B1-C38;A28-B1-C39; A28-B1-C40; A28-B1-C41; A28-B1-C42; A28-B1-C43; A28-B1-C44;A28-B1-C45; A28-B1-C46; A1-B2-C1; A1-B2-C2; A1-B2-C3; A1-B2-C4;A1-B2-C5; A1-B2-C6; A1-B2-C7; A1-B2-C8; A1-B2-C9; A1-B2-C10; A1-B2-C11;A1-B2-C12; A1-B2-C13; A1-B2-C14; A1-B2-C15; A1-B2-C16; A1-B2-C17;A1-B2-C18; A1-B2-C19; A1-B2-C20; A1-B2-C21; A1-B2-C22; A1-B2-C23;A1-B2-C24; A1-B2-C25; A1-B2-C26; A1-B2-C27; A1-B2-C28; A1-B2-C29;A1-B2-C30; A1-B2-C31; A1-B2-C32; A1-B2-C33; A1-B2-C34; A1-B2-C35;A1-B2-C36; A1-B2-C37; A1-B2-C38; A1-B2-C39; A1-B2-C40; A1-B2-C41;A1-B2-C42; A1-B2-C43; A1-B2-C44; A1-B2-C45; A1-B2-C46; A2-B2-C1;A2-B2-C2; A2-B2-C3; A2-B2-C4; A2-B2-C5; A2-B2-C6; A2-B2-C7; A2-B2-C8;A2-B2-C9; A2-B2-C10; A2-B2-C11; A2-B2-C12; A2-B2-C13; A2-B2-C14;A2-B2-C15; A2-B2-C16; A2-B2-C17; A2-B2-C18; A2-B2-C19; A2-B2-C20;A2-B2-C21; A2-B2-C22; A2-B2-C23; A2-B2-C24; A2-B2-C25; A2-B2-C26;A2-B2-C27; A2-B2-C28; A2-B2-C29; A2-B2-C30; A2-B2-C31; A2-B2-C32;A2-B2-C33; A2-B2-C34; A2-B2-C35; A2-B2-C36; A2-B2-C37; A2-B2-C38;A2-B2-C39; A2-B2-C40; A2-B2-C41; A2-B2-C42; A2-B2-C43; A2-B2-C44;A2-B2-C45; A2-B2-C46; A3-B2-C1; A3-B2-C2; A3-B2-C3; A3-B2-C4; A3-B2-C5;A3-B2-C6; A3-B2-C7; A3-B2-C8; A3-B2-C9; A3-B2-C10; A3-B2-C11; A3-B2-C12;A3-B2-C13; A3-B2-C14; A3-B2-C15; A3-B2-C16; A3-B2-C17; A3-B2-C18;A3-B2-C19; A3-B2-C20; A3-B2-C21; A3-B2-C22; A3-B2-C23; A3-B2-C24;A3-B2-C25; A3-B2-C26; A3-B2-C27; A3-B2-C28; A3-B2-C29; A3-B2-C30;A3-B2-C31; A3-B2-C32; A3-B2-C33; A3-B2-C34; A3-B2-C35; A3-B2-C36;A3-B2-C37; A3-B2-C38; A3-B2-C39; A3-B2-C40; A3-B2-C41; A3-B2-C42;A3-B2-C43; A3-B2-C44; A3-B2-C45; A3-B2-C46; A4-B2-C1; A4-B2-C2;A4-B2-C3; A4-B2-C4; A4-B2-C5; A4-B2-C6; A4-B2-C7; A4-B2-C8; A4-B2-C9;A4-B2-C10; A4-B2-C11; A4-B2-C12; A4-B2-C13; A4-B2-C14; A4-B2-C15;A4-B2-C16; A4-B2-C17; A4-B2-C18; A4-B2-C19; A4-B2-C20; A4-B2-C21;A4-B2-C22; A4-B2-C23; A4-B2-C24; A4-B2-C25; A4-B2-C26; A4-B2-C27;A4-B2-C28; A4-B2-C29; A4-B2-C30; A4-B2-C31; A4-B2-C32; A4-B2-C33;A4-B2-C34; A4-B2-C35; A4-B2-C36; A4-B2-C37; A4-B2-C38; A4-B2-C39;A4-B2-C40; A4-B2-C41; A4-B2-C42; A4-B2-C43; A4-B2-C44; A4-B2-C45;A4-B2-C46; A5-B2-C1; A5-B2-C2; A5-B2-C3; A5-B2-C4; A5-B2-C5; A5-B2-C6;A5-B2-C7; A5-B2-C8; A5-B2-C9; A5-B2-C10; A5-B2-C11; A5-B2-C12;A5-B2-C13; A5-B2-C14; A5-B2-C15; A5-B2-C16; A5-B2-C17; A5-B2-C18;A5-B2-C19; A5-B2-C20; A5-B2-C21; A5-B2-C22; A5-B2-C23; A5-B2-C24;A5-B2-C25; A5-B2-C26; A5-B2-C27; A5-B2-C28; A5-B2-C29; A5-B2-C30;A5-B2-C31; A5-B2-C32; A5-B2-C33; A5-B2-C34; A5-B2-C35; A5-B2-C36;A5-B2-C37; A5-B2-C38; A5-B2-C39; A5-B2-C40; A5-B2-C41; A5-B2-C42;A5-B2-C43; A5-B2-C44; A5-B2-C45; A5-B2-C46; A6-B2-C1; A6-B2-C2;A6-B2-C3; A6-B2-C4; A6-B2-C5; A6-B2-C6; A6-B2-C7; A6-B2-C8; A6-B2-C9;A6-B2-C10; A6-B2-C11; A6-B2-C12; A6-B2-C13; A6-B2-C14; A6-B2-C15;A6-B2-C16; A6-B2-C17; A6-B2-C18; A6-B2-C19; A6-B2-C20; A6-B2-C21;A6-B2-C22; A6-B2-C23; A6-B2-C24; A6-B2-C25; A6-B2-C26; A6-B2-C27;A6-B2-C28; A6-B2-C29; A6-B2-C30; A6-B2-C31; A6-B2-C32; A6-B2-C33;A6-B2-C34; A6-B2-C35; A6-B2-C36; A6-B2-C37; A6-B2-C38; A6-B2-C39;A6-B2-C40; A6-B2-C41; A6-B2-C42; A6-B2-C43; A6-B2-C44; A6-B2-C45;A6-B2-C46; A7-B2-C1; A7-B2-C2; A7-B2-C3; A7-B2-C4; A7-B2-C5; A7-B2-C6;A7-B2-C7; A7-B2-C8; A7-B2-C9; A7-B2-C10; A7-B2-C11; A7-B2-C12;A7-B2-C13; A7-B2-C14; A7-B2-C15; A7-B2-C16; A7-B2-C17; A7-B2-C18;A7-B2-C19; A7-B2-C20; A7-B2-C21; A7-B2-C22; A7-B2-C23; A7-B2-C24;A7-B2-C25; A7-B2-C26; A7-B2-C27; A7-B2-C28; A7-B2-C29; A7-B2-C30;A7-B2-C31; A7-B2-C32; A7-B2-C33; A7-B2-C34; A7-B2-C35; A7-B2-C36;A7-B2-C37; A7-B2-C38; A7-B2-C39; A7-B2-C40; A7-B2-C41; A7-B2-C42;A7-B2-C43; A7-B2-C44; A7-B2-C45; A7-B2-C46; A8-B2-C1; A8-B2-C2;A8-B2-C3; A8-B2-C4; A8-B2-C5; A8-B2-C6; A8-B2-C7; A8-B2-C8; A8-B2-C9;A8-B2-C10; A8-B2-C11; A8-B2-C12; A8-B2-C13; A8-B2-C14; A8-B2-C15;A8-B2-C16; A8-B2-C17; A8-B2-C18; A8-B2-C19; A8-B2-C20; A8-B2-C21;A8-B2-C22; A8-B2-C23; A8-B2-C24; A8-B2-C25; A8-B2-C26; A8-B2-C27;A8-B2-C28; A8-B2-C29; A8-B2-C30; A8-B2-C31; A8-B2-C32; A8-B2-C33;A8-B2-C34; A8-B2-C35; A8-B2-C36; A8-B2-C37; A8-B2-C38; A8-B2-C39;A8-B2-C40; A8-B2-C41; A8-B2-C42; A8-B2-C43; A8-B2-C44; A8-B2-C45;A8-B2-C46; A9-B2-C1; A9-B2-C2; A9-B2-C3; A9-B2-C4; A9-B2-C5; A9-B2-C6;A9-B2-C7; A9-B2-C8; A9-B2-C9; A9-B2-C10; A9-B2-C11; A9-B2-C12;A9-B2-C13; A9-B2-C14; A9-B2-C15; A9-B2-C16; A9-B2-C17; A9-B2-C18;A9-B2-C19; A9-B2-C20; A9-B2-C21; A9-B2-C22; A9-B2-C23; A9-B2-C24;A9-B2-C25; A9-B2-C26; A9-B2-C27; A9-B2-C28; A9-B2-C29; A9-B2-C30;A9-B2-C31; A9-B2-C32; A9-B2-C33; A9-B2-C34; A9-B2-C35; A9-B2-C36;A9-B2-C37; A9-B2-C38; A9-B2-C39; A9-B2-C40; A9-B2-C41; A9-B2-C42;A9-B2-C43; A9-B2-C44; A9-B2-C45; A9-B2-C46; A10-B2-C1; A10-B2-C2;A10-B2-C3; A10-B2-C4; A10-B2-C5; A10-B2-C6; A10-B2-C7; A10-B2-C8;A10-B2-C9; A10-B2-C10; A10-B2-C11; A10-B2-C12; A10-B2-C13; A10-B2-C14;A10-B2-C15; A10-B2-C16; A10-B2-C17; A10-B2-C18; A10-B2-C19; A10-B2-C20;A10-B2-C21; A10-B2-C22; A10-B2-C23; A10-B2-C24; A10-B2-C25; A10-B2-C26;A10-B2-C27; A10-B2-C28; A10-B2-C29; A10-B2-C30; A10-B2-C31; A10-B2-C32;A10-B2-C33; A10-B2-C34; A10-B2-C35; A10-B2-C36; A10-B2-C37; A10-B2-C38;A10-B2-C39; A10-B2-C40; A10-B2-C41; A10-B2-C42; A10-B2-C43; A10-B2-C44;A10-B2-C45; A10-B2-C46; A11-B2-C1; A11-B2-C2; A11-B2-C3; A11-B2-C4;A11-B2-C5; A11-B2-C6; A11-B2-C7; A11-B2-C8; A11-B2-C9; A11-B2-C10;A11-B2-C11; A11-B2-C12; A11-B2-C13; A11-B2-C14; A11-B2-C15; A11-B2-C16;A11-B2-C17; A11-B2-C18; A11-B2-C19; A11-B2-C20; A11-B2-C21; A11-B2-C22;A11-B2-C23; A11-B2-C24; A11-B2-C25; A11-B2-C26; A11-B2-C27; A11-B2-C28;A11-B2-C29; A11-B2-C30; A11-B2-C31; A11-B2-C32; A11-B2-C33; A11-B2-C34;A11-B2-C35; A11-B2-C36; A11-B2-C37; A11-B2-C38; A11-B2-C39; A11-B2-C40;A11-B2-C41; A11-B2-C42; A11-B2-C43; A11-B2-C44; A11-B2-C45; A11-B2-C46;A12-B2-C1; A12-B2-C2; A12-B2-C3; A12-B2-C4; A12-B2-C5; A12-B2-C6;A12-B2-C7; A12-B2-C8; A12-B2-C9; A12-B2-C10; A12-B2-C11; A12-B2-C12;A12-B2-C13; A12-B2-C14; A12-B2-C15; A12-B2-C16; A12-B2-C17; A12-B2-C18;A12-B2-C19; A12-B2-C20; A12-B2-C21; A12-B2-C22; A12-B2-C23; A12-B2-C24;A12-B2-C25; A12-B2-C26; A12-B2-C27; A12-B2-C28; A12-B2-C29; A12-B2-C30;A12-B2-C31; A12-B2-C32; A12-B2-C33; A12-B2-C34; A12-B2-C35; A12-B2-C36;A12-B2-C37; A12-B2-C38; A12-B2-C39; A12-B2-C40; A12-B2-C41; A12-B2-C42;A12-B2-C43; A12-B2-C44; A12-B2-C45; A12-B2-C46; A13-B2-C1; A13-B2-C2;A13-B2-C3; A13-B2-C4; A13-B2-C5; A13-B2-C6; A13-B2-C7; A13-B2-C8;A13-B2-C9; A13-B2-C10; A13-B2-C11; A13-B2-C12; A13-B2-C13; A13-B2-C14;A13-B2-C15; A13-B2-C16; A13-B2-C17; A13-B2-C18; A13-B2-C19; A13-B2-C20;A13-B2-C21; A13-B2-C22; A13-B2-C23; A13-B2-C24; A13-B2-C25; A13-B2-C26;A13-B2-C27; A13-B2-C28; A13-B2-C29; A13-B2-C30; A13-B2-C31; A13-B2-C32;A13-B2-C33; A13-B2-C34; A13-B2-C35; A13-B2-C36; A13-B2-C37; A13-B2-C38;A13-B2-C39; A13-B2-C40; A13-B2-C41; A13-B2-C42; A13-B2-C43; A13-B2-C44;A13-B2-C45; A13-B2-C46; A14-B2-C1; A14-B2-C2; A14-B2-C3; A14-B2-C4;A14-B2-C5; A14-B2-C6; A14-B2-C7; A14-B2-C8; A14-B2-C9; A14-B2-C10;A14-B2-C11; A14-B2-C12; A14-B2-C13; A14-B2-C14; A14-B2-C15; A14-B2-C16;A14-B2-C17; A14-B2-C18; A14-B2-C19; A14-B2-C20; A14-B2-C21; A14-B2-C22;A14-B2-C23; A14-B2-C24; A14-B2-C25; A14-B2-C26; A14-B2-C27; A14-B2-C28;A14-B2-C29; A14-B2-C30; A14-B2-C31; A14-B2-C32; A14-B2-C33; A14-B2-C34;A14-B2-C35; A14-B2-C36; A14-B2-C37; A14-B2-C38; A14-B2-C39; A14-B2-C40;A14-B2-C41; A14-B2-C42; A14-B2-C43; A14-B2-C44; A14-B2-C45; A14-B2-C46;A15-B2-C1; A15-B2-C2; A15-B2-C3; A15-B2-C4; A15-B2-C5; A15-B2-C6;A15-B2-C7; A15-B2-C8; A15-B2-C9; A15-B2-C10; A15-B2-C11; A15-B2-C12;A15-B2-C13; A15-B2-C14; A15-B2-C15; A15-B2-C16; A15-B2-C17; A15-B2-C18;A15-B2-C19; A15-B2-C20; A15-B2-C21; A15-B2-C22; A15-B2-C23; A15-B2-C24;A15-B2-C25; A15-B2-C26; A15-B2-C27; A15-B2-C28; A15-B2-C29; A15-B2-C30;A15-B2-C31; A15-B2-C32; A15-B2-C33; A15-B2-C34; A15-B2-C35; A15-B2-C36;A15-B2-C37; A15-B2-C38; A15-B2-C39; A15-B2-C40; A15-B2-C41; A15-B2-C42;A15-B2-C43; A15-B2-C44; A15-B2-C45; A15-B2-C46; A16-B2-C1; A16-B2-C2;A16-B2-C3; A16-B2-C4; A16-B2-C5; A16-B2-C6; A16-B2-C7; A16-B2-C8;A16-B2-C9; A16-B2-C10; A16-B2-C11; A16-B2-C12; A16-B2-C13; A16-B2-C14;A16-B2-C15; A16-B2-C16; A16-B2-C17; A16-B2-C18; A16-B2-C19; A16-B2-C20;A16-B2-C21; A16-B2-C22; A16-B2-C23; A16-B2-C24; A16-B2-C25; A16-B2-C26;A16-B2-C27; A16-B2-C28; A16-B2-C29; A16-B2-C30; A16-B2-C31; A16-B2-C32;A16-B2-C33; A16-B2-C34; A16-B2-C35; A16-B2-C36; A16-B2-C37; A16-B2-C38;A16-B2-C39; A16-B2-C40; A16-B2-C41; A16-B2-C42; A16-B2-C43; A16-B2-C44;A16-B2-C45; A16-B2-C46; A17-B2-C1; A17-B2-C2; A17-B2-C3; A17-B2-C4;A17-B2-C5; A17-B2-C6; A17-B2-C7; A17-B2-C8; A17-B2-C9; A17-B2-C10;A17-B2-C11; A17-B2-C12; A17-B2-C13; A17-B2-C14; A17-B2-C15; A17-B2-C16;A17-B2-C17; A17-B2-C18; A17-B2-C19; A17-B2-C20; A17-B2-C21; A17-B2-C22;A17-B2-C23; A17-B2-C24; A17-B2-C25; A17-B2-C26; A17-B2-C27; A17-B2-C28;A17-B2-C29; A17-B2-C30; A17-B2-C31; A17-B2-C32; A17-B2-C33; A17-B2-C34;A17-B2-C35; A17-B2-C36; A17-B2-C37; A17-B2-C38; A17-B2-C39; A17-B2-C40;A17-B2-C41; A17-B2-C42; A17-B2-C43; A17-B2-C44; A17-B2-C45; A17-B2-C46;A18-B2-C1; A18-B2-C2; A18-B2-C3; A18-B2-C4; A18-B2-C5; A18-B2-C6;A18-B2-C7; A18-B2-C8; A18-B2-C9; A18-B2-C10; A18-B2-C11; A18-B2-C12;A18-B2-C13; A18-B2-C14; A18-B2-C15; A18-B2-C16; A18-B2-C17; A18-B2-C18;A18-B2-C19; A18-B2-C20; A18-B2-C21; A18-B2-C22; A18-B2-C23; A18-B2-C24;A18-B2-C25; A18-B2-C26; A18-B2-C27; A18-B2-C28; A18-B2-C29; A18-B2-C30;A18-B2-C31; A18-B2-C32; A18-B2-C33; A18-B2-C34; A18-B2-C35; A18-B2-C36;A18-B2-C37; A18-B2-C38; A18-B2-C39; A18-B2-C40; A18-B2-C41; A18-B2-C42;A18-B2-C43; A18-B2-C44; A18-B2-C45; A18-B2-C46; A19-B2-C1; A19-B2-C2;A19-B2-C3; A19-B2-C4; A19-B2-C5; A19-B2-C6; A19-B2-C7; A19-B2-C8;A19-B2-C9; A19-B2-C10; A19-B2-C11; A19-B2-C12; A19-B2-C13; A19-B2-C14;A19-B2-C15; A19-B2-C16; A19-B2-C17; A19-B2-C18; A19-B2-C19; A19-B2-C20;A19-B2-C21; A19-B2-C22; A19-B2-C23; A19-B2-C24; A19-B2-C25; A19-B2-C26;A19-B2-C27; A19-B2-C28; A19-B2-C29; A19-B2-C30; A19-B2-C31; A19-B2-C32;A19-B2-C33; A19-B2-C34; A19-B2-C35; A19-B2-C36; A19-B2-C37; A19-B2-C38;A19-B2-C39; A19-B2-C40; A19-B2-C41; A19-B2-C42; A19-B2-C43; A19-B2-C44;A19-B2-C45; A19-B2-C46; A20-B2-C1; A20-B2-C2; A20-B2-C3; A20-B2-C4;A20-B2-C5; A20-B2-C6; A20-B2-C7; A20-B2-C8; A20-B2-C9; A20-B2-C10;A20-B2-C11; A20-B2-C12; A20-B2-C13; A20-B2-C14; A20-B2-C15; A20-B2-C16;A20-B2-C17; A20-B2-C18; A20-B2-C19; A20-B2-C20; A20-B2-C21; A20-B2-C22;A20-B2-C23; A20-B2-C24; A20-B2-C25; A20-B2-C26; A20-B2-C27; A20-B2-C28;A20-B2-C29; A20-B2-C30; A20-B2-C31; A20-B2-C32; A20-B2-C33; A20-B2-C34;A20-B2-C35; A20-B2-C36; A20-B2-C37; A20-B2-C38; A20-B2-C39; A20-B2-C40;A20-B2-C41; A20-B2-C42; A20-B2-C43; A20-B2-C44; A20-B2-C45; A20-B2-C46;A21-B2-C1; A21-B2-C2; A21-B2-C3; A21-B2-C4; A21-B2-C5; A21-B2-C6;A21-B2-C7; A21-B2-C8; A21-B2-C9; A21-B2-C10; A21-B2-C11; A21-B2-C12;A21-B2-C13; A21-B2-C14; A21-B2-C15; A21-B2-C16; A21-B2-C17; A21-B2-C18;A21-B2-C19; A21-B2-C20; A21-B2-C21; A21-B2-C22; A21-B2-C23; A21-B2-C24;A21-B2-C25; A21-B2-C26; A21-B2-C27; A21-B2-C28; A21-B2-C29; A21-B2-C30;A21-B2-C31; A21-B2-C32; A21-B2-C33; A21-B2-C34; A21-B2-C35; A21-B2-C36;A21-B2-C37; A21-B2-C38; A21-B2-C39; A21-B2-C40; A21-B2-C41; A21-B2-C42;A21-B2-C43; A21-B2-C44; A21-B2-C45; A21-B2-C46; A22-B2-C1; A22-B2-C2;A22-B2-C3; A22-B2-C4; A22-B2-C5; A22-B2-C6; A22-B2-C7; A22-B2-C8;A22-B2-C9; A22-B2-C10; A22-B2-C11; A22-B2-C12; A22-B2-C13; A22-B2-C14;A22-B2-C15; A22-B2-C16; A22-B2-C17; A22-B2-C18; A22-B2-C19; A22-B2-C20;A22-B2-C21; A22-B2-C22; A22-B2-C23; A22-B2-C24; A22-B2-C25; A22-B2-C26;A22-B2-C27; A22-B2-C28; A22-B2-C29; A22-B2-C30; A22-B2-C31; A22-B2-C32;A22-B2-C33; A22-B2-C34; A22-B2-C35; A22-B2-C36; A22-B2-C37; A22-B2-C38;A22-B2-C39; A22-B2-C40; A22-B2-C41; A22-B2-C42; A22-B2-C43; A22-B2-C44;A22-B2-C45; A22-B2-C46; A23-B2-C1; A23-B2-C2; A23-B2-C3; A23-B2-C4;A23-B2-C5; A23-B2-C6; A23-B2-C7; A23-B2-C8; A23-B2-C9; A23-B2-C10;A23-B2-C11; A23-B2-C12; A23-B2-C13; A23-B2-C14; A23-B2-C15; A23-B2-C16;A23-B2-C17; A23-B2-C18; A23-B2-C19; A23-B2-C20; A23-B2-C21; A23-B2-C22;A23-B2-C23; A23-B2-C24; A23-B2-C25; A23-B2-C26; A23-B2-C27; A23-B2-C28;A23-B2-C29; A23-B2-C30; A23-B2-C31; A23-B2-C32; A23-B2-C33; A23-B2-C34;A23-B2-C35; A23-B2-C36; A23-B2-C37; A23-B2-C38; A23-B2-C39; A23-B2-C40;A23-B2-C41; A23-B2-C42; A23-B2-C43; A23-B2-C44; A23-B2-C45; A23-B2-C46;A24-B2-C1; A24-B2-C2; A24-B2-C3; A24-B2-C4; A24-B2-C5; A24-B2-C6;A24-B2-C7; A24-B2-C8; A24-B2-C9; A24-B2-C10; A24-B2-C11; A24-B2-C12;A24-B2-C13; A24-B2-C14; A24-B2-C15; A24-B2-C16; A24-B2-C17; A24-B2-C18;A24-B2-C19; A24-B2-C20; A24-B2-C21; A24-B2-C22; A24-B2-C23; A24-B2-C24;A24-B2-C25; A24-B2-C26; A24-B2-C27; A24-B2-C28; A24-B2-C29; A24-B2-C30;A24-B2-C31; A24-B2-C32; A24-B2-C33; A24-B2-C34; A24-B2-C35; A24-B2-C36;A24-B2-C37; A24-B2-C38; A24-B2-C39; A24-B2-C40; A24-B2-C41; A24-B2-C42;A24-B2-C43; A24-B2-C44; A24-B2-C45; A24-B2-C46; A25-B2-C1; A25-B2-C2;A25-B2-C3; A25-B2-C4; A25-B2-C5; A25-B2-C6; A25-B2-C7; A25-B2-C8;A25-B2-C9; A25-B2-C10; A25-B2-C11; A25-B2-C12; A25-B2-C13; A25-B2-C14;A25-B2-C15; A25-B2-C16; A25-B2-C17; A25-B2-C18; A25-B2-C19; A25-B2-C20;A25-B2-C21; A25-B2-C22; A25-B2-C23; A25-B2-C24; A25-B2-C25; A25-B2-C26;A25-B2-C27; A25-B2-C28; A25-B2-C29; A25-B2-C30; A25-B2-C31; A25-B2-C32;A25-B2-C33; A25-B2-C34; A25-B2-C35; A25-B2-C36; A25-B2-C37; A25-B2-C38;A25-B2-C39; A25-B2-C40; A25-B2-C41; A25-B2-C42; A25-B2-C43; A25-B2-C44;A25-B2-C45; A25-B2-C46; A26-B2-C1; A26-B2-C2; A26-B2-C3; A26-B2-C4;A26-B2-C5; A26-B2-C6; A26-B2-C7; A26-B2-C8; A26-B2-C9; A26-B2-C10;A26-B2-C11; A26-B2-C12; A26-B2-C13; A26-B2-C14; A26-B2-C15; A26-B2-C16;A26-B2-C17; A26-B2-C18; A26-B2-C19; A26-B2-C20; A26-B2-C21; A26-B2-C22;A26-B2-C23; A26-B2-C24; A26-B2-C25; A26-B2-C26; A26-B2-C27; A26-B2-C28;A26-B2-C29; A26-B2-C30; A26-B2-C31; A26-B2-C32; A26-B2-C33; A26-B2-C34;A26-B2-C35; A26-B2-C36; A26-B2-C37; A26-B2-C38; A26-B2-C39; A26-B2-C40;A26-B2-C41; A26-B2-C42; A26-B2-C43; A26-B2-C44; A26-B2-C45; A26-B2-C46;A27-B2-C1; A27-B2-C2; A27-B2-C3; A27-B2-C4; A27-B2-C5; A27-B2-C6;A27-B2-C7; A27-B2-C8; A27-B2-C9; A27-B2-C10; A27-B2-C11; A27-B2-C12;A27-B2-C13; A27-B2-C14; A27-B2-C15; A27-B2-C16; A27-B2-C17; A27-B2-C18;A27-B2-C19; A27-B2-C20; A27-B2-C21; A27-B2-C22; A27-B2-C23; A27-B2-C24;A27-B2-C25; A27-B2-C26; A27-B2-C27; A27-B2-C28; A27-B2-C29; A27-B2-C30;A27-B2-C31; A27-B2-C32; A27-B2-C33; A27-B2-C34; A27-B2-C35; A27-B2-C36;A27-B2-C37; A27-B2-C38; A27-B2-C39; A27-B2-C40; A27-B2-C41; A27-B2-C42;A27-B2-C43; A27-B2-C44; A27-B2-C45; A27-B2-C46; A28-B2-C1; A28-B2-C2;A28-B2-C3; A28-B2-C4; A28-B2-C5; A28-B2-C6; A28-B2-C7; A28-B2-C8;A28-B2-C9; A28-B2-C10; A28-B2-C11; A28-B2-C12; A28-B2-C13; A28-B2-C14;A28-B2-C15; A28-B2-C16; A28-B2-C17; A28-B2-C18; A28-B2-C19; A28-B2-C20;A28-B2-C21; A28-B2-C22; A28-B2-C23; A28-B2-C24; A28-B2-C25; A28-B2-C26;A28-B2-C27; A28-B2-C28; A28-B2-C29; A28-B2-C30; A28-B2-C31; A28-B2-C32;A28-B2-C33; A28-B2-C34; A28-B2-C35; A28-B2-C36; A28-B2-C37; A28-B2-C38;A28-B2-C39; A28-B2-C40; A28-B2-C41; A28-B2-C42; A28-B2-C43; A28-B2-C44;A28-B2-C45; A28-B2-C46; A1-B3-C1; A1-B3-C2; A1-B3-C3; A1-B3-C4;A1-B3-C5; A1-B3-C6; A1-B3-C7; A1-B3-C8; A1-B3-C9; A1-B3-C10; A1-B3-C11;A1-B3-C12; A1-B3-C13; A1-B3-C14; A1-B3-C15; A1-B3-C16; A1-B3-C17;A1-B3-C18; A1-B3-C19; A1-B3-C20; A1-B3-C21; A1-B3-C22; A1-B3-C23;A1-B3-C24; A1-B3-C25; A1-B3-C26; A1-B3-C27; A1-B3-C28; A1-B3-C29;A1-B3-C30; A1-B3-C31; A1-B3-C32; A1-B3-C33; A1-B3-C34; A1-B3-C35;A1-B3-C36; A1-B3-C37; A1-B3-C38; A1-B3-C39; A1-B3-C40; A1-B3-C41;A1-B3-C42; A1-B3-C43; A1-B3-C44; A1-B3-C45; A1-B3-C46; A2-B3-C1;A2-B3-C2; A2-B3-C3; A2-B3-C4; A2-B3-C5; A2-B3-C6; A2-B3-C7; A2-B3-C8;A2-B3-C9; A2-B3-C10; A2-B3-C11; A2-B3-C12; A2-B3-C13; A2-B3-C14;A2-B3-C15; A2-B3-C16; A2-B3-C17; A2-B3-C18; A2-B3-C19; A2-B3-C20;A2-B3-C21; A2-B3-C22; A2-B3-C23; A2-B3-C24; A2-B3-C25; A2-B3-C26;A2-B3-C27; A2-B3-C28; A2-B3-C29; A2-B3-C30; A2-B3-C31; A2-B3-C32;A2-B3-C33; A2-B3-C34; A2-B3-C35; A2-B3-C36; A2-B3-C37; A2-B3-C38;A2-B3-C39; A2-B3-C40; A2-B3-C41; A2-B3-C42; A2-B3-C43; A2-B3-C44;A2-B3-C45; A2-B3-C46; A3-B3-C1; A3-B3-C2; A3-B3-C3; A3-B3-C4; A3-B3-C5;A3-B3-C6; A3-B3-C7; A3-B3-C8; A3-B3-C9; A3-B3-C10; A3-B3-C11; A3-B3-C12;A3-B3-C13; A3-B3-C14; A3-B3-C15; A3-B3-C16; A3-B3-C17; A3-B3-C18;A3-B3-C19; A3-B3-C20; A3-B3-C21; A3-B3-C22; A3-B3-C23; A3-B3-C24;A3-B3-C25; A3-B3-C26; A3-B3-C27; A3-B3-C28; A3-B3-C29; A3-B3-C30;A3-B3-C31; A3-B3-C32; A3-B3-C33; A3-B3-C34; A3-B3-C35; A3-B3-C36;A3-B3-C37; A3-B3-C38; A3-B3-C39; A3-B3-C40; A3-B3-C41; A3-B3-C42;A3-B3-C43; A3-B3-C44; A3-B3-C45; A3-B3-C46; A4-B3-C1; A4-B3-C2;A4-B3-C3; A4-B3-C4; A4-B3-C5; A4-B3-C6; A4-B3-C7; A4-B3-C8; A4-B3-C9;A4-B3-C10; A4-B3-C11; A4-B3-C12; A4-B3-C13; A4-B3-C14; A4-B3-C15;A4-B3-C16; A4-B3-C17; A4-B3-C18; A4-B3-C19; A4-B3-C20; A4-B3-C21;A4-B3-C22; A4-B3-C23; A4-B3-C24; A4-B3-C25; A4-B3-C26; A4-B3-C27;A4-B3-C28; A4-B3-C29; A4-B3-C30; A4-B3-C31; A4-B3-C32; A4-B3-C33;A4-B3-C34; A4-B3-C35; A4-B3-C36; A4-B3-C37; A4-B3-C38; A4-B3-C39;A4-B3-C40; A4-B3-C41; A4-B3-C42; A4-B3-C43; A4-B3-C44; A4-B3-C45;A4-B3-C46; A5-B3-C1; A5-B3-C2; A5-B3-C3; A5-B3-C4; A5-B3-C5; A5-B3-C6;A5-B3-C7; A5-B3-C8; A5-B3-C9; A5-B3-C10; A5-B3-C11; A5-B3-C12;A5-B3-C13; A5-B3-C14; A5-B3-C15; A5-B3-C16; A5-B3-C17; A5-B3-C18;A5-B3-C19; A5-B3-C20; A5-B3-C21; A5-B3-C22; A5-B3-C23; A5-B3-C24;A5-B3-C25; A5-B3-C26; A5-B3-C27; A5-B3-C28; A5-B3-C29; A5-B3-C30;A5-B3-C31; A5-B3-C32; A5-B3-C33; A5-B3-C34; A5-B3-C35; A5-B3-C36;A5-B3-C37; A5-B3-C38; A5-B3-C39; A5-B3-C40; A5-B3-C41; A5-B3-C42;A5-B3-C43; A5-B3-C44; A5-B3-C45; A5-B3-C46; A6-B3-C1; A6-B3-C2;A6-B3-C3; A6-B3-C4; A6-B3-C5; A6-B3-C6; A6-B3-C7; A6-B3-C8; A6-B3-C9;A6-B3-C10; A6-B3-C11; A6-B3-C12; A6-B3-C13; A6-B3-C14; A6-B3-C15;A6-B3-C16; A6-B3-C17; A6-B3-C18; A6-B3-C19; A6-B3-C20; A6-B3-C21;A6-B3-C22; A6-B3-C23; A6-B3-C24; A6-B3-C25; A6-B3-C26; A6-B3-C27;A6-B3-C28; A6-B3-C29; A6-B3-C30; A6-B3-C31; A6-B3-C32; A6-B3-C33;A6-B3-C34; A6-B3-C35; A6-B3-C36; A6-B3-C37; A6-B3-C38; A6-B3-C39;A6-B3-C40; A6-B3-C41; A6-B3-C42; A6-B3-C43; A6-B3-C44; A6-B3-C45;A6-B3-C46; A7-B3-C1; A7-B3-C2; A7-B3-C3; A7-B3-C4; A7-B3-C5; A7-B3-C6;A7-B3-C7; A7-B3-C8; A7-B3-C9; A7-B3-C10; A7-B3-C11; A7-B3-C12;A7-B3-C13; A7-B3-C14; A7-B3-C15; A7-B3-C16; A7-B3-C17; A7-B3-C18;A7-B3-C19; A7-B3-C20; A7-B3-C21; A7-B3-C22; A7-B3-C23; A7-B3-C24;A7-B3-C25; A7-B3-C26; A7-B3-C27; A7-B3-C28; A7-B3-C29; A7-B3-C30;A7-B3-C31; A7-B3-C32; A7-B3-C33; A7-B3-C34; A7-B3-C35; A7-B3-C36;A7-B3-C37; A7-B3-C38; A7-B3-C39; A7-B3-C40; A7-B3-C41; A7-B3-C42;A7-B3-C43; A7-B3-C44; A7-B3-C45; A7-B3-C46; A8-B3-C1; A8-B3-C2;A8-B3-C3; A8-B3-C4; A8-B3-C5; A8-B3-C6; A8-B3-C7; A8-B3-C8; A8-B3-C9;A8-B3-C10; A8-B3-C11; A8-B3-C12; A8-B3-C13; A8-B3-C14; A8-B3-C15;A8-B3-C16; A8-B3-C17; A8-B3-C18; A8-B3-C19; A8-B3-C20; A8-B3-C21;A8-B3-C22; A8-B3-C23; A8-B3-C24; A8-B3-C25; A8-B3-C26; A8-B3-C27;A8-B3-C28; A8-B3-C29; A8-B3-C30; A8-B3-C31; A8-B3-C32; A8-B3-C33;A8-B3-C34; A8-B3-C35; A8-B3-C36; A8-B3-C37; A8-B3-C38; A8-B3-C39;A8-B3-C40; A8-B3-C41; A8-B3-C42; A8-B3-C43; A8-B3-C44; A8-B3-C45;A8-B3-C46; A9-B3-C1; A9-B3-C2; A9-B3-C3; A9-B3-C4; A9-B3-C5; A9-B3-C6;A9-B3-C7; A9-B3-C8; A9-B3-C9; A9-B3-C10; A9-B3-C11; A9-B3-C12;A9-B3-C13; A9-B3-C14; A9-B3-C15; A9-B3-C16; A9-B3-C17; A9-B3-C18;A9-B3-C19; A9-B3-C20; A9-B3-C21; A9-B3-C22; A9-B3-C23; A9-B3-C24;A9-B3-C25; A9-B3-C26; A9-B3-C27; A9-B3-C28; A9-B3-C29; A9-B3-C30;A9-B3-C31; A9-B3-C32; A9-B3-C33; A9-B3-C34; A9-B3-C35; A9-B3-C36;A9-B3-C37; A9-B3-C38; A9-B3-C39; A9-B3-C40; A9-B3-C41; A9-B3-C42;A9-B3-C43; A9-B3-C44; A9-B3-C45; A9-B3-C46; A10-B3-C1; A10-B3-C2;A10-B3-C3; A10-B3-C4; A10-B3-C5; A10-B3-C6; A10-B3-C7; A10-B3-C8;A10-B3-C9; A10-B3-C10; A10-B3-C11; A10-B3-C12; A10-B3-C13; A10-B3-C14;A10-B3-C15; A10-B3-C16; A10-B3-C17; A10-B3-C18; A10-B3-C19; A10-B3-C20;A10-B3-C21; A10-B3-C22; A10-B3-C23; A10-B3-C24; A10-B3-C25; A10-B3-C26;A10-B3-C27; A10-B3-C28; A10-B3-C29; A10-B3-C30; A10-B3-C31; A10-B3-C32;A10-B3-C33; A10-B3-C34; A10-B3-C35; A10-B3-C36; A10-B3-C37; A10-B3-C38;A10-B3-C39; A10-B3-C40; A10-B3-C41; A10-B3-C42; A10-B3-C43; A10-B3-C44;A10-B3-C45; A10-B3-C46; A11-B3-C1; A11-B3-C2; A11-B3-C3; A11-B3-C4;A11-B3-C5; A11-B3-C6; A11-B3-C7; A11-B3-C8; A11-B3-C9; A11-B3-C10;A11-B3-C11; A11-B3-C12; A11-B3-C13; A11-B3-C14; A11-B3-C15; A11-B3-C16;A11-B3-C17; A11-B3-C18; A11-B3-C19; A11-B3-C20; A11-B3-C21; A11-B3-C22;A11-B3-C23; A11-B3-C24; A11-B3-C25; A11-B3-C26; A11-B3-C27; A11-B3-C28;A11-B3-C29; A11-B3-C30; A11-B3-C31; A11-B3-C32; A11-B3-C33; A11-B3-C34;A11-B3-C35; A11-B3-C36; A11-B3-C37; A11-B3-C38; A11-B3-C39; A11-B3-C40;A11-B3-C41; A11-B3-C42; A11-B3-C43; A11-B3-C44; A11-B3-C45; A11-B3-C46;A12-B3-C1; A12-B3-C2; A12-B3-C3; A12-B3-C4; A12-B3-C5; A12-B3-C6;A12-B3-C7; A12-B3-C8; A12-B3-C9; A12-B3-C10; A12-B3-C11; A12-B3-C12;A12-B3-C13; A12-B3-C14; A12-B3-C15; A12-B3-C16; A12-B3-C17; A12-B3-C18;A12-B3-C19; A12-B3-C20; A12-B3-C21; A12-B3-C22; A12-B3-C23; A12-B3-C24;A12-B3-C25; A12-B3-C26; A12-B3-C27; A12-B3-C28; A12-B3-C29; A12-B3-C30;A12-B3-C31; A12-B3-C32; A12-B3-C33; A12-B3-C34; A12-B3-C35; A12-B3-C36;A12-B3-C37; A12-B3-C38; A12-B3-C39; A12-B3-C40; A12-B3-C41; A12-B3-C42;A12-B3-C43; A12-B3-C44; A12-B3-C45; A12-B3-C46; A13-B3-C1; A13-B3-C2;A13-B3-C3; A13-B3-C4; A13-B3-C5; A13-B3-C6; A13-B3-C7; A13-B3-C8;A13-B3-C9; A13-B3-C10; A13-B3-C11; A13-B3-C12; A13-B3-C13; A13-B3-C14;A13-B3-C15; A13-B3-C16; A13-B3-C17; A13-B3-C18; A13-B3-C19; A13-B3-C20;A13-B3-C21; A13-B3-C22; A13-B3-C23; A13-B3-C24; A13-B3-C25; A13-B3-C26;A13-B3-C27; A13-B3-C28; A13-B3-C29; A13-B3-C30; A13-B3-C31; A13-B3-C32;A13-B3-C33; A13-B3-C34; A13-B3-C35; A13-B3-C36; A13-B3-C37; A13-B3-C38;A13-B3-C39; A13-B3-C40; A13-B3-C41; A13-B3-C42; A13-B3-C43; A13-B3-C44;A13-B3-C45; A13-B3-C46; A14-B3-C1; A14-B3-C2; A14-B3-C3; A14-B3-C4;A14-B3-C5; A14-B3-C6; A14-B3-C7; A14-B3-C8; A14-B3-C9; A14-B3-C10;A14-B3-C11; A14-B3-C12; A14-B3-C13; A14-B3-C14; A14-B3-C15; A14-B3-C16;A14-B3-C17; A14-B3-C18; A14-B3-C19; A14-B3-C20; A14-B3-C21; A14-B3-C22;A14-B3-C23; A14-B3-C24; A14-B3-C25; A14-B3-C26; A14-B3-C27; A14-B3-C28;A14-B3-C29; A14-B3-C30; A14-B3-C31; A14-B3-C32; A14-B3-C33; A14-B3-C34;A14-B3-C35; A14-B3-C36; A14-B3-C37; A14-B3-C38; A14-B3-C39; A14-B3-C40;A14-B3-C41; A14-B3-C42; A14-B3-C43; A14-B3-C44; A14-B3-C45; A14-B3-C46;A15-B3-C1; A15-B3-C2; A15-B3-C3; A15-B3-C4; A15-B3-C5; A15-B3-C6;A15-B3-C7; A15-B3-C8; A15-B3-C9; A15-B3-C10; A15-B3-C11; A15-B3-C12;A15-B3-C13; A15-B3-C14; A15-B3-C15; A15-B3-C16; A15-B3-C17; A15-B3-C18;A15-B3-C19; A15-B3-C20; A15-B3-C21; A15-B3-C22; A15-B3-C23; A15-B3-C24;A15-B3-C25; A15-B3-C26; A15-B3-C27; A15-B3-C28; A15-B3-C29; A15-B3-C30;A15-B3-C31; A15-B3-C32; A15-B3-C33; A15-B3-C34; A15-B3-C35; A15-B3-C36;A15-B3-C37; A15-B3-C38; A15-B3-C39; A15-B3-C40; A15-B3-C41; A15-B3-C42;A15-B3-C43; A15-B3-C44; A15-B3-C45; A15-B3-C46; A16-B3-C1; A16-B3-C2;A16-B3-C3; A16-B3-C4; A16-B3-C5; A16-B3-C6; A16-B3-C7; A16-B3-C8;A16-B3-C9; A16-B3-C10; A16-B3-C11; A16-B3-C12; A16-B3-C13; A16-B3-C14;A16-B3-C15; A16-B3-C16; A16-B3-C17; A16-B3-C18; A16-B3-C19; A16-B3-C20;A16-B3-C21; A16-B3-C22; A16-B3-C23; A16-B3-C24; A16-B3-C25; A16-B3-C26;A16-B3-C27; A16-B3-C28; A16-B3-C29; A16-B3-C30; A16-B3-C31; A16-B3-C32;A16-B3-C33; A16-B3-C34; A16-B3-C35; A16-B3-C36; A16-B3-C37; A16-B3-C38;A16-B3-C39; A16-B3-C40; A16-B3-C41; A16-B3-C42; A16-B3-C43; A16-B3-C44;A16-B3-C45; A16-B3-C46; A17-B3-C1; A17-B3-C2; A17-B3-C3; A17-B3-C4;A17-B3-C5; A17-B3-C6; A17-B3-C7; A17-B3-C8; A17-B3-C9; A17-B3-C10;A17-B3-C11; A17-B3-C12; A17-B3-C13; A17-B3-C14; A17-B3-C15; A17-B3-C16;A17-B3-C17; A17-B3-C18; A17-B3-C19; A17-B3-C20; A17-B3-C21; A17-B3-C22;A17-B3-C23; A17-B3-C24; A17-B3-C25; A17-B3-C26; A17-B3-C27; A17-B3-C28;A17-B3-C29; A17-B3-C30; A17-B3-C31; A17-B3-C32; A17-B3-C33; A17-B3-C34;A17-B3-C35; A17-B3-C36; A17-B3-C37; A17-B3-C38; A17-B3-C39; A17-B3-C40;A17-B3-C41; A17-B3-C42; A17-B3-C43; A17-B3-C44; A17-B3-C45; A17-B3-C46;A18-B3-C1; A18-B3-C2; A18-B3-C3; A18-B3-C4; A18-B3-C5; A18-B3-C6;A18-B3-C7; A18-B3-C8; A18-B3-C9; A18-B3-C10; A18-B3-C11; A18-B3-C12;A18-B3-C13; A18-B3-C14; A18-B3-C15; A18-B3-C16; A18-B3-C17; A18-B3-C18;A18-B3-C19; A18-B3-C20; A18-B3-C21; A18-B3-C22; A18-B3-C23; A18-B3-C24;A18-B3-C25; A18-B3-C26; A18-B3-C27; A18-B3-C28; A18-B3-C29; A18-B3-C30;A18-B3-C31; A18-B3-C32; A18-B3-C33; A18-B3-C34; A18-B3-C35; A18-B3-C36;A18-B3-C37; A18-B3-C38; A18-B3-C39; A18-B3-C40; A18-B3-C41; A18-B3-C42;A18-B3-C43; A18-B3-C44; A18-B3-C45; A18-B3-C46; A19-B3-C1; A19-B3-C2;A19-B3-C3; A19-B3-C4; A19-B3-C5; A19-B3-C6; A19-B3-C7; A19-B3-C8;A19-B3-C9; A19-B3-C10; A19-B3-C11; A19-B3-C12; A19-B3-C13; A19-B3-C14;A19-B3-C15; A19-B3-C16; A19-B3-C17; A19-B3-C18; A19-B3-C19; A19-B3-C20;A19-B3-C21; A19-B3-C22; A19-B3-C23; A19-B3-C24; A19-B3-C25; A19-B3-C26;A19-B3-C27; A19-B3-C28; A19-B3-C29; A19-B3-C30; A19-B3-C31; A19-B3-C32;A19-B3-C33; A19-B3-C34; A19-B3-C35; A19-B3-C36; A19-B3-C37; A19-B3-C38;A19-B3-C39; A19-B3-C40; A19-B3-C41; A19-B3-C42; A19-B3-C43; A19-B3-C44;A19-B3-C45; A19-B3-C46; A20-B3-C1; A20-B3-C2; A20-B3-C3; A20-B3-C4;A20-B3-C5; A20-B3-C6; A20-B3-C7; A20-B3-C8; A20-B3-C9; A20-B3-C10;A20-B3-C11; A20-B3-C12; A20-B3-C13; A20-B3-C14; A20-B3-C15; A20-B3-C16;A20-B3-C17; A20-B3-C18; A20-B3-C19; A20-B3-C20; A20-B3-C21; A20-B3-C22;A20-B3-C23; A20-B3-C24; A20-B3-C25; A20-B3-C26; A20-B3-C27; A20-B3-C28;A20-B3-C29; A20-B3-C30; A20-B3-C31; A20-B3-C32; A20-B3-C33; A20-B3-C34;A20-B3-C35; A20-B3-C36; A20-B3-C37; A20-B3-C38; A20-B3-C39; A20-B3-C40;A20-B3-C41; A20-B3-C42; A20-B3-C43; A20-B3-C44; A20-B3-C45; A20-B3-C46;A21-B3-C1; A21-B3-C2; A21-B3-C3; A21-B3-C4; A21-B3-C5; A21-B3-C6;A21-B3-C7; A21-B3-C8; A21-B3-C9; A21-B3-C10; A21-B3-C11; A21-B3-C12;A21-B3-C13; A21-B3-C14; A21-B3-C15; A21-B3-C16; A21-B3-C17; A21-B3-C18;A21-B3-C19; A21-B3-C20; A21-B3-C21; A21-B3-C22; A21-B3-C23; A21-B3-C24;A21-B3-C25; A21-B3-C26; A21-B3-C27; A21-B3-C28; A21-B3-C29; A21-B3-C30;A21-B3-C31; A21-B3-C32; A21-B3-C33; A21-B3-C34; A21-B3-C35; A21-B3-C36;A21-B3-C37; A21-B3-C38; A21-B3-C39; A21-B3-C40; A21-B3-C41; A21-B3-C42;A21-B3-C43; A21-B3-C44; A21-B3-C45; A21-B3-C46; A22-B3-C1; A22-B3-C2;A22-B3-C3; A22-B3-C4; A22-B3-C5; A22-B3-C6; A22-B3-C7; A22-B3-C8;A22-B3-C9; A22-B3-C10; A22-B3-C11; A22-B3-C12; A22-B3-C13; A22-B3-C14;A22-B3-C15; A22-B3-C16; A22-B3-C17; A22-B3-C18; A22-B3-C19; A22-B3-C20;A22-B3-C21; A22-B3-C22; A22-B3-C23; A22-B3-C24; A22-B3-C25; A22-B3-C26;A22-B3-C27; A22-B3-C28; A22-B3-C29; A22-B3-C30; A22-B3-C31; A22-B3-C32;A22-B3-C33; A22-B3-C34; A22-B3-C35; A22-B3-C36; A22-B3-C37; A22-B3-C38;A22-B3-C39; A22-B3-C40; A22-B3-C41; A22-B3-C42; A22-B3-C43; A22-B3-C44;A22-B3-C45; A22-B3-C46; A23-B3-C1; A23-B3-C2; A23-B3-C3; A23-B3-C4;A23-B3-C5; A23-B3-C6; A23-B3-C7; A23-B3-C8; A23-B3-C9; A23-B3-C10;A23-B3-C11; A23-B3-C12; A23-B3-C13; A23-B3-C14; A23-B3-C15; A23-B3-C16;A23-B3-C17; A23-B3-C18; A23-B3-C19; A23-B3-C20; A23-B3-C21; A23-B3-C22;A23-B3-C23; A23-B3-C24; A23-B3-C25; A23-B3-C26; A23-B3-C27; A23-B3-C28;A23-B3-C29; A23-B3-C30; A23-B3-C31; A23-B3-C32; A23-B3-C33; A23-B3-C34;A23-B3-C35; A23-B3-C36; A23-B3-C37; A23-B3-C38; A23-B3-C39; A23-B3-C40;A23-B3-C41; A23-B3-C42; A23-B3-C43; A23-B3-C44; A23-B3-C45; A23-B3-C46;A24-B3-C1; A24-B3-C2; A24-B3-C3; A24-B3-C4; A24-B3-C5; A24-B3-C6;A24-B3-C7; A24-B3-C8; A24-B3-C9; A24-B3-C10; A24-B3-C11; A24-B3-C12;A24-B3-C13; A24-B3-C14; A24-B3-C15; A24-B3-C16; A24-B3-C17; A24-B3-C18;A24-B3-C19; A24-B3-C20; A24-B3-C21; A24-B3-C22; A24-B3-C23; A24-B3-C24;A24-B3-C25; A24-B3-C26; A24-B3-C27; A24-B3-C28; A24-B3-C29; A24-B3-C30;A24-B3-C31; A24-B3-C32; A24-B3-C33; A24-B3-C34; A24-B3-C35; A24-B3-C36;A24-B3-C37; A24-B3-C38; A24-B3-C39; A24-B3-C40; A24-B3-C41; A24-B3-C42;A24-B3-C43; A24-B3-C44; A24-B3-C45; A24-B3-C46; A25-B3-C1; A25-B3-C2;A25-B3-C3; A25-B3-C4; A25-B3-C5; A25-B3-C6; A25-B3-C7; A25-B3-C8;A25-B3-C9; A25-B3-C10; A25-B3-C11; A25-B3-C12; A25-B3-C13; A25-B3-C14;A25-B3-C15; A25-B3-C16; A25-B3-C17; A25-B3-C18; A25-B3-C19; A25-B3-C20;A25-B3-C21; A25-B3-C22; A25-B3-C23; A25-B3-C24; A25-B3-C25; A25-B3-C26;A25-B3-C27; A25-B3-C28; A25-B3-C29; A25-B3-C30; A25-B3-C31; A25-B3-C32;A25-B3-C33; A25-B3-C34; A25-B3-C35; A25-B3-C36; A25-B3-C37; A25-B3-C38;A25-B3-C39; A25-B3-C40; A25-B3-C41; A25-B3-C42; A25-B3-C43; A25-B3-C44;A25-B3-C45; A25-B3-C46; A26-B3-C1; A26-B3-C2; A26-B3-C3; A26-B3-C4;A26-B3-C5; A26-B3-C6; A26-B3-C7; A26-B3-C8; A26-B3-C9; A26-B3-C10;A26-B3-C11; A26-B3-C12; A26-B3-C13; A26-B3-C14; A26-B3-C15; A26-B3-C16;A26-B3-C17; A26-B3-C18; A26-B3-C19; A26-B3-C20; A26-B3-C21; A26-B3-C22;A26-B3-C23; A26-B3-C24; A26-B3-C25; A26-B3-C26; A26-B3-C27; A26-B3-C28;A26-B3-C29; A26-B3-C30; A26-B3-C31; A26-B3-C32; A26-B3-C33; A26-B3-C34;A26-B3-C35; A26-B3-C36; A26-B3-C37; A26-B3-C38; A26-B3-C39; A26-B3-C40;A26-B3-C41; A26-B3-C42; A26-B3-C43; A26-B3-C44; A26-B3-C45; A26-B3-C46;A27-B3-C1; A27-B3-C2; A27-B3-C3; A27-B3-C4; A27-B3-C5; A27-B3-C6;A27-B3-C7; A27-B3-C8; A27-B3-C9; A27-B3-C10; A27-B3-C11; A27-B3-C12;A27-B3-C13; A27-B3-C14; A27-B3-C15; A27-B3-C16; A27-B3-C17; A27-B3-C18;A27-B3-C19; A27-B3-C20; A27-B3-C21; A27-B3-C22; A27-B3-C23; A27-B3-C24;A27-B3-C25; A27-B3-C26; A27-B3-C27; A27-B3-C28; A27-B3-C29; A27-B3-C30;A27-B3-C31; A27-B3-C32; A27-B3-C33; A27-B3-C34; A27-B3-C35; A27-B3-C36;A27-B3-C37; A27-B3-C38; A27-B3-C39; A27-B3-C40; A27-B3-C41; A27-B3-C42;A27-B3-C43; A27-B3-C44; A27-B3-C45; A27-B3-C46; A28-B3-C1; A28-B3-C2;A28-B3-C3; A28-B3-C4; A28-B3-C5; A28-B3-C6; A28-B3-C7; A28-B3-C8;A28-B3-C9; A28-B3-C10; A28-B3-C11; A28-B3-C12; A28-B3-C13; A28-B3-C14;A28-B3-C15; A28-B3-C16; A28-B3-C17; A28-B3-C18; A28-B3-C19; A28-B3-C20;A28-B3-C21; A28-B3-C22; A28-B3-C23; A28-B3-C24; A28-B3-C25; A28-B3-C26;A28-B3-C27; A28-B3-C28; A28-B3-C29; A28-B3-C30; A28-B3-C31; A28-B3-C32;A28-B3-C33; A28-B3-C34; A28-B3-C35; A28-B3-C36; A28-B3-C37; A28-B3-C38;A28-B3-C39; A28-B3-C40; A28-B3-C41; A28-B3-C42; A28-B3-C43; A28-B3-C44;A28-B3-C45; A28-B3-C46; A1-B4-C1; A1-B4-C2; A1-B4-C3; A1-B4-C4;A1-B4-C5; A1-B4-C6; A1-B4-C7; A1-B4-C8; A1-B4-C9; A1-B4-C10; A1-B4-C11;A1-B4-C12; A1-B4-C13; A1-B4-C14; A1-B4-C15; A1-B4-C16; A1-B4-C17;A1-B4-C18; A1-B4-C19; A1-B4-C20; A1-B4-C21; A1-B4-C22; A1-B4-C23;A1-B4-C24; A1-B4-C25; A1-B4-C26; A1-B4-C27; A1-B4-C28; A1-B4-C29;A1-B4-C30; A1-B4-C31; A1-B4-C32; A1-B4-C33; A1-B4-C34; A1-B4-C35;A1-B4-C36; A1-B4-C37; A1-B4-C38; A1-B4-C39; A1-B4-C40; A1-B4-C41;A1-B4-C42; A1-B4-C43; A1-B4-C44; A1-B4-C45; A1-B4-C46; A2-B4-C1;A2-B4-C2; A2-B4-C3; A2-B4-C4; A2-B4-C5; A2-B4-C6; A2-B4-C7; A2-B4-C8;A2-B4-C9; A2-B4-C10; A2-B4-C11; A2-B4-C12; A2-B4-C13; A2-B4-C14;A2-B4-C15; A2-B4-C16; A2-B4-C17; A2-B4-C18; A2-B4-C19; A2-B4-C20;A2-B4-C21; A2-B4-C22; A2-B4-C23; A2-B4-C24; A2-B4-C25; A2-B4-C26;A2-B4-C27; A2-B4-C28; A2-B4-C29; A2-B4-C30; A2-B4-C31; A2-B4-C32;A2-B4-C33; A2-B4-C34; A2-B4-C35; A2-B4-C36; A2-B4-C37; A2-B4-C38;A2-B4-C39; A2-B4-C40; A2-B4-C41; A2-B4-C42; A2-B4-C43; A2-B4-C44;A2-B4-C45; A2-B4-C46; A3-B4-C1; A3-B4-C2; A3-B4-C3; A3-B4-C4; A3-B4-C5;A3-B4-C6; A3-B4-C7; A3-B4-C8; A3-B4-C9; A3-B4-C10; A3-B4-C11; A3-B4-C12;A3-B4-C13; A3-B4-C14; A3-B4-C15; A3-B4-C16; A3-B4-C17; A3-B4-C18;A3-B4-C19; A3-B4-C20; A3-B4-C21; A3-B4-C22; A3-B4-C23; A3-B4-C24;A3-B4-C25; A3-B4-C26; A3-B4-C27; A3-B4-C28; A3-B4-C29; A3-B4-C30;A3-B4-C31; A3-B4-C32; A3-B4-C33; A3-B4-C34; A3-B4-C35; A3-B4-C36;A3-B4-C37; A3-B4-C38; A3-B4-C39; A3-B4-C40; A3-B4-C41; A3-B4-C42;A3-B4-C43; A3-B4-C44; A3-B4-C45; A3-B4-C46; A4-B4-C1; A4-B4-C2;A4-B4-C3; A4-B4-C4; A4-B4-C5; A4-B4-C6; A4-B4-C7; A4-B4-C8; A4-B4-C9;A4-B4-C10; A4-B4-C11; A4-B4-C12; A4-B4-C13; A4-B4-C14; A4-B4-C15;A4-B4-C16; A4-B4-C17; A4-B4-C18; A4-B4-C19; A4-B4-C20; A4-B4-C21;A4-B4-C22; A4-B4-C23; A4-B4-C24; A4-B4-C25; A4-B4-C26; A4-B4-C27;A4-B4-C28; A4-B4-C29; A4-B4-C30; A4-B4-C31; A4-B4-C32; A4-B4-C33;A4-B4-C34; A4-B4-C35; A4-B4-C36; A4-B4-C37; A4-B4-C38; A4-B4-C39;A4-B4-C40; A4-B4-C41; A4-B4-C42; A4-B4-C43; A4-B4-C44; A4-B4-C45;A4-B4-C46; A5-B4-C1; A5-B4-C2; A5-B4-C3; A5-B4-C4; A5-B4-C5; A5-B4-C6;A5-B4-C7; A5-B4-C8; A5-B4-C9; A5-B4-C10; A5-B4-C11; A5-B4-C12;A5-B4-C13; A5-B4-C14; A5-B4-C15; A5-B4-C16; A5-B4-C17; A5-B4-C18;A5-B4-C19; A5-B4-C20; A5-B4-C21; A5-B4-C22; A5-B4-C23; A5-B4-C24;A5-B4-C25; A5-B4-C26; A5-B4-C27; A5-B4-C28; A5-B4-C29; A5-B4-C30;A5-B4-C31; A5-B4-C32; A5-B4-C33; A5-B4-C34; A5-B4-C35; A5-B4-C36;A5-B4-C37; A5-B4-C38; A5-B4-C39; A5-B4-C40; A5-B4-C41; A5-B4-C42;A5-B4-C43; A5-B4-C44; A5-B4-C45; A5-B4-C46; A6-B4-C1; A6-B4-C2;A6-B4-C3; A6-B4-C4; A6-B4-C5; A6-B4-C6; A6-B4-C7; A6-B4-C8; A6-B4-C9;A6-B4-C10; A6-B4-C11; A6-B4-C12; A6-B4-C13; A6-B4-C14; A6-B4-C15;A6-B4-C16; A6-B4-C17; A6-B4-C18; A6-B4-C19; A6-B4-C20; A6-B4-C21;A6-B4-C22; A6-B4-C23; A6-B4-C24; A6-B4-C25; A6-B4-C26; A6-B4-C27;A6-B4-C28; A6-B4-C29; A6-B4-C30; A6-B4-C31; A6-B4-C32; A6-B4-C33;A6-B4-C34; A6-B4-C35; A6-B4-C36; A6-B4-C37; A6-B4-C38; A6-B4-C39;A6-B4-C40; A6-B4-C41; A6-B4-C42; A6-B4-C43; A6-B4-C44; A6-B4-C45;A6-B4-C46; A7-B4-C1; A7-B4-C2; A7-B4-C3; A7-B4-C4; A7-B4-C5; A7-B4-C6;A7-B4-C7; A7-B4-C8; A7-B4-C9; A7-B4-C10; A7-B4-C11; A7-B4-C12;A7-B4-C13; A7-B4-C14; A7-B4-C15; A7-B4-C16; A7-B4-C17; A7-B4-C18;A7-B4-C19; A7-B4-C20; A7-B4-C21; A7-B4-C22; A7-B4-C23; A7-B4-C24;A7-B4-C25; A7-B4-C26; A7-B4-C27; A7-B4-C28; A7-B4-C29; A7-B4-C30;A7-B4-C31; A7-B4-C32; A7-B4-C33; A7-B4-C34; A7-B4-C35; A7-B4-C36;A7-B4-C37; A7-B4-C38; A7-B4-C39; A7-B4-C40; A7-B4-C41; A7-B4-C42;A7-B4-C43; A7-B4-C44; A7-B4-C45; A7-B4-C46; A8-B4-C1; A8-B4-C2;A8-B4-C3; A8-B4-C4; A8-B4-C5; A8-B4-C6; A8-B4-C7; A8-B4-C8; A8-B4-C9;A8-B4-C10; A8-B4-C11; A8-B4-C12; A8-B4-C13; A8-B4-C14; A8-B4-C15;A8-B4-C16; A8-B4-C17; A8-B4-C18; A8-B4-C19; A8-B4-C20; A8-B4-C21;A8-B4-C22; A8-B4-C23; A8-B4-C24; A8-B4-C25; A8-B4-C26; A8-B4-C27;A8-B4-C28; A8-B4-C29; A8-B4-C30; A8-B4-C31; A8-B4-C32; A8-B4-C33;A8-B4-C34; A8-B4-C35; A8-B4-C36; A8-B4-C37; A8-B4-C38; A8-B4-C39;A8-B4-C40; A8-B4-C41; A8-B4-C42; A8-B4-C43; A8-B4-C44; A8-B4-C45;A8-B4-C46; A9-B4-C1; A9-B4-C2; A9-B4-C3; A9-B4-C4; A9-B4-C5; A9-B4-C6;A9-B4-C7; A9-B4-C8; A9-B4-C9; A9-B4-C10; A9-B4-C11; A9-B4-C12;A9-B4-C13; A9-B4-C14; A9-B4-C15; A9-B4-C16; A9-B4-C17; A9-B4-C18;A9-B4-C19; A9-B4-C20; A9-B4-C21; A9-B4-C22; A9-B4-C23; A9-B4-C24;A9-B4-C25; A9-B4-C26; A9-B4-C27; A9-B4-C28; A9-B4-C29; A9-B4-C30;A9-B4-C31; A9-B4-C32; A9-B4-C33; A9-B4-C34; A9-B4-C35; A9-B4-C36;A9-B4-C37; A9-B4-C38; A9-B4-C39; A9-B4-C40; A9-B4-C41; A9-B4-C42;A9-B4-C43; A9-B4-C44; A9-B4-C45; A9-B4-C46; A10-B4-C1; A10-B4-C2;A10-B4-C3; A10-B4-C4; A10-B4-C5; A10-B4-C6; A10-B4-C7; A10-B4-C8;A10-B4-C9; A10-B4-C10; A10-B4-C11; A10-B4-C12; A10-B4-C13; A10-B4-C14;A10-B4-C15; A10-B4-C16; A10-B4-C17; A10-B4-C18; A10-B4-C19; A10-B4-C20;A10-B4-C21; A10-B4-C22; A10-B4-C23; A10-B4-C24; A10-B4-C25; A10-B4-C26;A10-B4-C27; A10-B4-C28; A10-B4-C29; A10-B4-C30; A10-B4-C31; A10-B4-C32;A10-B4-C33; A10-B4-C34; A10-B4-C35; A10-B4-C36; A10-B4-C37; A10-B4-C38;A10-B4-C39; A10-B4-C40; A10-B4-C41; A10-B4-C42; A10-B4-C43; A10-B4-C44;A10-B4-C45; A10-B4-C46; A11-B4-C1; A11-B4-C2; A11-B4-C3; A11-B4-C4;A11-B4-C5; A11-B4-C6; A11-B4-C7; A11-B4-C8; A11-B4-C9; A11-B4-C10;A11-B4-C11; A11-B4-C12; A11-B4-C13; A11-B4-C14; A11-B4-C15; A11-B4-C16;A11-B4-C17; A11-B4-C18; A11-B4-C19; A11-B4-C20; A11-B4-C21; A11-B4-C22;A11-B4-C23; A11-B4-C24; A11-B4-C25; A11-B4-C26; A11-B4-C27; A11-B4-C28;A11-B4-C29; A11-B4-C30; A11-B4-C31; A11-B4-C32; A11-B4-C33; A11-B4-C34;A11-B4-C35; A11-B4-C36; A11-B4-C37; A11-B4-C38; A11-B4-C39; A11-B4-C40;A11-B4-C41; A11-B4-C42; A11-B4-C43; A11-B4-C44; A11-B4-C45; A11-B4-C46;A12-B4-C1; A12-B4-C2; A12-B4-C3; A12-B4-C4; A12-B4-C5; A12-B4-C6;A12-B4-C7; A12-B4-C8; A12-B4-C9; A12-B4-C10; A12-B4-C11; A12-B4-C12;A12-B4-C13; A12-B4-C14; A12-B4-C15; A12-B4-C16; A12-B4-C17; A12-B4-C18;A12-B4-C19; A12-B4-C20; A12-B4-C21; A12-B4-C22; A12-B4-C23; A12-B4-C24;A12-B4-C25; A12-B4-C26; A12-B4-C27; A12-B4-C28; A12-B4-C29; A12-B4-C30;A12-B4-C31; A12-B4-C32; A12-B4-C33; A12-B4-C34; A12-B4-C35; A12-B4-C36;A12-B4-C37; A12-B4-C38; A12-B4-C39; A12-B4-C40; A12-B4-C41; A12-B4-C42;A12-B4-C43; A12-B4-C44; A12-B4-C45; A12-B4-C46; A13-B4-C1; A13-B4-C2;A13-B4-C3; A13-B4-C4; A13-B4-C5; A13-B4-C6; A13-B4-C7; A13-B4-C8;A13-B4-C9; A13-B4-C10; A13-B4-C11; A13-B4-C12; A13-B4-C13; A13-B4-C14;A13-B4-C15; A13-B4-C16; A13-B4-C17; A13-B4-C18; A13-B4-C19; A13-B4-C20;A13-B4-C21; A13-B4-C22; A13-B4-C23; A13-B4-C24; A13-B4-C25; A13-B4-C26;A13-B4-C27; A13-B4-C28; A13-B4-C29; A13-B4-C30; A13-B4-C31; A13-B4-C32;A13-B4-C33; A13-B4-C34; A13-B4-C35; A13-B4-C36; A13-B4-C37; A13-B4-C38;A13-B4-C39; A13-B4-C40; A13-B4-C41; A13-B4-C42; A13-B4-C43; A13-B4-C44;A13-B4-C45; A13-B4-C46; A14-B4-C1; A14-B4-C2; A14-B4-C3; A14-B4-C4;A14-B4-C5; A14-B4-C6; A14-B4-C7; A14-B4-C8; A14-B4-C9; A14-B4-C10;A14-B4-C11; A14-B4-C12; A14-B4-C13; A14-B4-C14; A14-B4-C15; A14-B4-C16;A14-B4-C17; A14-B4-C18; A14-B4-C19; A14-B4-C20; A14-B4-C21; A14-B4-C22;A14-B4-C23; A14-B4-C24; A14-B4-C25; A14-B4-C26; A14-B4-C27; A14-B4-C28;A14-B4-C29; A14-B4-C30; A14-B4-C31; A14-B4-C32; A14-B4-C33; A14-B4-C34;A14-B4-C35; A14-B4-C36; A14-B4-C37; A14-B4-C38; A14-B4-C39; A14-B4-C40;A14-B4-C41; A14-B4-C42; A14-B4-C43; A14-B4-C44; A14-B4-C45; A14-B4-C46;A15-B4-C1; A15-B4-C2; A15-B4-C3; A15-B4-C4; A15-B4-C5; A15-B4-C6;A15-B4-C7; A15-B4-C8; A15-B4-C9; A15-B4-C10; A15-B4-C11; A15-B4-C12;A15-B4-C13; A15-B4-C14; A15-B4-C15; A15-B4-C16; A15-B4-C17; A15-B4-C18;A15-B4-C19; A15-B4-C20; A15-B4-C21; A15-B4-C22; A15-B4-C23; A15-B4-C24;A15-B4-C25; A15-B4-C26; A15-B4-C27; A15-B4-C28; A15-B4-C29; A15-B4-C30;A15-B4-C31; A15-B4-C32; A15-B4-C33; A15-B4-C34; A15-B4-C35; A15-B4-C36;A15-B4-C37; A15-B4-C38; A15-B4-C39; A15-B4-C40; A15-B4-C41; A15-B4-C42;A15-B4-C43; A15-B4-C44; A15-B4-C45; A15-B4-C46; A16-B4-C1; A16-B4-C2;A16-B4-C3; A16-B4-C4; A16-B4-C5; A16-B4-C6; A16-B4-C7; A16-B4-C8;A16-B4-C9; A16-B4-C10; A16-B4-C11; A16-B4-C12; A16-B4-C13; A16-B4-C14;A16-B4-C15; A16-B4-C16; A16-B4-C17; A16-B4-C18; A16-B4-C19; A16-B4-C20;A16-B4-C21; A16-B4-C22; A16-B4-C23; A16-B4-C24; A16-B4-C25; A16-B4-C26;A16-B4-C27; A16-B4-C28; A16-B4-C29; A16-B4-C30; A16-B4-C31; A16-B4-C32;A16-B4-C33; A16-B4-C34; A16-B4-C35; A16-B4-C36; A16-B4-C37; A16-B4-C38;A16-B4-C39; A16-B4-C40; A16-B4-C41; A16-B4-C42; A16-B4-C43; A16-B4-C44;A16-B4-C45; A16-B4-C46; A17-B4-C1; A17-B4-C2; A17-B4-C3; A17-B4-C4;A17-B4-C5; A17-B4-C6; A17-B4-C7; A17-B4-C8; A17-B4-C9; A17-B4-C10;A17-B4-C11; A17-B4-C12; A17-B4-C13; A17-B4-C14; A17-B4-C15; A17-B4-C16;A17-B4-C17; A17-B4-C18; A17-B4-C19; A17-B4-C20; A17-B4-C21; A17-B4-C22;A17-B4-C23; A17-B4-C24; A17-B4-C25; A17-B4-C26; A17-B4-C27; A17-B4-C28;A17-B4-C29; A17-B4-C30; A17-B4-C31; A17-B4-C32; A17-B4-C33; A17-B4-C34;A17-B4-C35; A17-B4-C36; A17-B4-C37; A17-B4-C38; A17-B4-C39; A17-B4-C40;A17-B4-C41; A17-B4-C42; A17-B4-C43; A17-B4-C44; A17-B4-C45; A17-B4-C46;A18-B4-C1; A18-B4-C2; A18-B4-C3; A18-B4-C4; A18-B4-C5; A18-B4-C6;A18-B4-C7; A18-B4-C8; A18-B4-C9; A18-B4-C10; A18-B4-C11; A18-B4-C12;A18-B4-C13; A18-B4-C14; A18-B4-C15; A18-B4-C16; A18-B4-C17; A18-B4-C18;A18-B4-C19; A18-B4-C20; A18-B4-C21; A18-B4-C22; A18-B4-C23; A18-B4-C24;A18-B4-C25; A18-B4-C26; A18-B4-C27; A18-B4-C28; A18-B4-C29; A18-B4-C30;A18-B4-C31; A18-B4-C32; A18-B4-C33; A18-B4-C34; A18-B4-C35; A18-B4-C36;A18-B4-C37; A18-B4-C38; A18-B4-C39; A18-B4-C40; A18-B4-C41; A18-B4-C42;A18-B4-C43; A18-B4-C44; A18-B4-C45; A18-B4-C46; A19-B4-C1; A19-B4-C2;A19-B4-C3; A19-B4-C4; A19-B4-C5; A19-B4-C6; A19-B4-C7; A19-B4-C8;A19-B4-C9; A19-B4-C10; A19-B4-C11; A19-B4-C12; A19-B4-C13; A19-B4-C14;A19-B4-C15; A19-B4-C16; A19-B4-C17; A19-B4-C18; A19-B4-C19; A19-B4-C20;A19-B4-C21; A19-B4-C22; A19-B4-C23; A19-B4-C24; A19-B4-C25; A19-B4-C26;A19-B4-C27; A19-B4-C28; A19-B4-C29; A19-B4-C30; A19-B4-C31; A19-B4-C32;A19-B4-C33; A19-B4-C34; A19-B4-C35; A19-B4-C36; A19-B4-C37; A19-B4-C38;A19-B4-C39; A19-B4-C40; A19-B4-C41; A19-B4-C42; A19-B4-C43; A19-B4-C44;A19-B4-C45; A19-B4-C46; A20-B4-C1; A20-B4-C2; A20-B4-C3; A20-B4-C4;A20-B4-C5; A20-B4-C6; A20-B4-C7; A20-B4-C8; A20-B4-C9; A20-B4-C10;A20-B4-C11; A20-B4-C12; A20-B4-C13; A20-B4-C14; A20-B4-C15; A20-B4-C16;A20-B4-C17; A20-B4-C18; A20-B4-C19; A20-B4-C20; A20-B4-C21; A20-B4-C22;A20-B4-C23; A20-B4-C24; A20-B4-C25; A20-B4-C26; A20-B4-C27; A20-B4-C28;A20-B4-C29; A20-B4-C30; A20-B4-C31; A20-B4-C32; A20-B4-C33; A20-B4-C34;A20-B4-C35; A20-B4-C36; A20-B4-C37; A20-B4-C38; A20-B4-C39; A20-B4-C40;A20-B4-C41; A20-B4-C42; A20-B4-C43; A20-B4-C44; A20-B4-C45; A20-B4-C46;A21-B4-C1; A21-B4-C2; A21-B4-C3; A21-B4-C4; A21-B4-C5; A21-B4-C6;A21-B4-C7; A21-B4-C8; A21-B4-C9; A21-B4-C10; A21-B4-C11; A21-B4-C12;A21-B4-C13; A21-B4-C14; A21-B4-C15; A21-B4-C16; A21-B4-C17; A21-B4-C18;A21-B4-C19; A21-B4-C20; A21-B4-C21; A21-B4-C22; A21-B4-C23; A21-B4-C24;A21-B4-C25; A21-B4-C26; A21-B4-C27; A21-B4-C28; A21-B4-C29; A21-B4-C30;A21-B4-C31; A21-B4-C32; A21-B4-C33; A21-B4-C34; A21-B4-C35; A21-B4-C36;A21-B4-C37; A21-B4-C38; A21-B4-C39; A21-B4-C40; A21-B4-C41; A21-B4-C42;A21-B4-C43; A21-B4-C44; A21-B4-C45; A21-B4-C46; A22-B4-C1; A22-B4-C2;A22-B4-C3; A22-B4-C4; A22-B4-C5; A22-B4-C6; A22-B4-C7; A22-B4-C8;A22-B4-C9; A22-B4-C10; A22-B4-C11; A22-B4-C12; A22-B4-C13; A22-B4-C14;A22-B4-C15; A22-B4-C16; A22-B4-C17; A22-B4-C18; A22-B4-C19; A22-B4-C20;A22-B4-C21; A22-B4-C22; A22-B4-C23; A22-B4-C24; A22-B4-C25; A22-B4-C26;A22-B4-C27; A22-B4-C28; A22-B4-C29; A22-B4-C30; A22-B4-C31; A22-B4-C32;A22-B4-C33; A22-B4-C34; A22-B4-C35; A22-B4-C36; A22-B4-C37; A22-B4-C38;A22-B4-C39; A22-B4-C40; A22-B4-C41; A22-B4-C42; A22-B4-C43; A22-B4-C44;A22-B4-C45; A22-B4-C46; A23-B4-C1; A23-B4-C2; A23-B4-C3; A23-B4-C4;A23-B4-C5; A23-B4-C6; A23-B4-C7; A23-B4-C8; A23-B4-C9; A23-B4-C10;A23-B4-C11; A23-B4-C12; A23-B4-C13; A23-B4-C14; A23-B4-C15; A23-B4-C16;A23-B4-C17; A23-B4-C18; A23-B4-C19; A23-B4-C20; A23-B4-C21; A23-B4-C22;A23-B4-C23; A23-B4-C24; A23-B4-C25; A23-B4-C26; A23-B4-C27; A23-B4-C28;A23-B4-C29; A23-B4-C30; A23-B4-C31; A23-B4-C32; A23-B4-C33; A23-B4-C34;A23-B4-C35; A23-B4-C36; A23-B4-C37; A23-B4-C38; A23-B4-C39; A23-B4-C40;A23-B4-C41; A23-B4-C42; A23-B4-C43; A23-B4-C44; A23-B4-C45; A23-B4-C46;A24-B4-C1; A24-B4-C2; A24-B4-C3; A24-B4-C4; A24-B4-C5; A24-B4-C6;A24-B4-C7; A24-B4-C8; A24-B4-C9; A24-B4-C10; A24-B4-C11; A24-B4-C12;A24-B4-C13; A24-B4-C14; A24-B4-C15; A24-B4-C16; A24-B4-C17; A24-B4-C18;A24-B4-C19; A24-B4-C20; A24-B4-C21; A24-B4-C22; A24-B4-C23; A24-B4-C24;A24-B4-C25; A24-B4-C26; A24-B4-C27; A24-B4-C28; A24-B4-C29; A24-B4-C30;A24-B4-C31; A24-B4-C32; A24-B4-C33; A24-B4-C34; A24-B4-C35; A24-B4-C36;A24-B4-C37; A24-B4-C38; A24-B4-C39; A24-B4-C40; A24-B4-C41; A24-B4-C42;A24-B4-C43; A24-B4-C44; A24-B4-C45; A24-B4-C46; A25-B4-C1; A25-B4-C2;A25-B4-C3; A25-B4-C4; A25-B4-C5; A25-B4-C6; A25-B4-C7; A25-B4-C8;A25-B4-C9; A25-B4-C10; A25-B4-C11; A25-B4-C12; A25-B4-C13; A25-B4-C14;A25-B4-C15; A25-B4-C16; A25-B4-C17; A25-B4-C18; A25-B4-C19; A25-B4-C20;A25-B4-C21; A25-B4-C22; A25-B4-C23; A25-B4-C24; A25-B4-C25; A25-B4-C26;A25-B4-C27; A25-B4-C28; A25-B4-C29; A25-B4-C30; A25-B4-C31; A25-B4-C32;A25-B4-C33; A25-B4-C34; A25-B4-C35; A25-B4-C36; A25-B4-C37; A25-B4-C38;A25-B4-C39; A25-B4-C40; A25-B4-C41; A25-B4-C42; A25-B4-C43; A25-B4-C44;A25-B4-C45; A25-B4-C46; A26-B4-C1; A26-B4-C2; A26-B4-C3; A26-B4-C4;A26-B4-C5; A26-B4-C6; A26-B4-C7; A26-B4-C8; A26-B4-C9; A26-B4-C10;A26-B4-C11; A26-B4-C12; A26-B4-C13; A26-B4-C14; A26-B4-C15; A26-B4-C16;A26-B4-C17; A26-B4-C18; A26-B4-C19; A26-B4-C20; A26-B4-C21; A26-B4-C22;A26-B4-C23; A26-B4-C24; A26-B4-C25; A26-B4-C26; A26-B4-C27; A26-B4-C28;A26-B4-C29; A26-B4-C30; A26-B4-C31; A26-B4-C32; A26-B4-C33; A26-B4-C34;A26-B4-C35; A26-B4-C36; A26-B4-C37; A26-B4-C38; A26-B4-C39; A26-B4-C40;A26-B4-C41; A26-B4-C42; A26-B4-C43; A26-B4-C44; A26-B4-C45; A26-B4-C46;A27-B4-C1; A27-B4-C2; A27-B4-C3; A27-B4-C4; A27-B4-C5; A27-B4-C6;A27-B4-C7; A27-B4-C8; A27-B4-C9; A27-B4-C10; A27-B4-C11; A27-B4-C12;A27-B4-C13; A27-B4-C14; A27-B4-C15; A27-B4-C16; A27-B4-C17; A27-B4-C18;A27-B4-C19; A27-B4-C20; A27-B4-C21; A27-B4-C22; A27-B4-C23; A27-B4-C24;A27-B4-C25; A27-B4-C26; A27-B4-C27; A27-B4-C28; A27-B4-C29; A27-B4-C30;A27-B4-C31; A27-B4-C32; A27-B4-C33; A27-B4-C34; A27-B4-C35; A27-B4-C36;A27-B4-C37; A27-B4-C38; A27-B4-C39; A27-B4-C40; A27-B4-C41; A27-B4-C42;A27-B4-C43; A27-B4-C44; A27-B4-C45; A27-B4-C46; A28-B4-C1; A28-B4-C2;A28-B4-C3; A28-B4-C4; A28-B4-C5; A28-B4-C6; A28-B4-C7; A28-B4-C8;A28-B4-C9; A28-B4-C10; A28-B4-C11; A28-B4-C12; A28-B4-C13; A28-B4-C14;A28-B4-C15; A28-B4-C16; A28-B4-C17; A28-B4-C18; A28-B4-C19; A28-B4-C20;A28-B4-C21; A28-B4-C22; A28-B4-C23; A28-B4-C24; A28-B4-C25; A28-B4-C26;A28-B4-C27; A28-B4-C28; A28-B4-C29; A28-B4-C30; A28-B4-C31; A28-B4-C32;A28-B4-C33; A28-B4-C34; A28-B4-C35; A28-B4-C36; A28-B4-C37; A28-B4-C38;A28-B4-C39; A28-B4-C40; A28-B4-C41; A28-B4-C42; A28-B4-C43; A28-B4-C44;A28-B4-C45; A28-B4-C46; A1-B5-C1; A1-B5-C2; A1-B5-C3; A1-B5-C4;A1-B5-C5; A1-B5-C6; A1-B5-C7; A1-B5-C8; A1-B5-C9; A1-B5-C10; A1-B5-C11;A1-B5-C12; A1-B5-C13; A1-B5-C14; A1-B5-C15; A1-B5-C16; A1-B5-C17;A1-B5-C18; A1-B5-C19; A1-B5-C20; A1-B5-C21; A1-B5-C22; A1-B5-C23;A1-B5-C24; A1-B5-C25; A1-B5-C26; A1-B5-C27; A1-B5-C28; A1-B5-C29;A1-B5-C30; A1-B5-C31; A1-B5-C32; A1-B5-C33; A1-B5-C34; A1-B5-C35;A1-B5-C36; A1-B5-C37; A1-B5-C38; A1-B5-C39; A1-B5-C40; A1-B5-C41;A1-B5-C42; A1-B5-C43; A1-B5-C44; A1-B5-C45; A1-B5-C46; A2-B5-C1;A2-B5-C2; A2-B5-C3; A2-B5-C4; A2-B5-C5; A2-B5-C6; A2-B5-C7; A2-B5-C8;A2-B5-C9; A2-B5-C10; A2-B5-C11; A2-B5-C12; A2-B5-C13; A2-B5-C14;A2-B5-C15; A2-B5-C16; A2-B5-C17; A2-B5-C18; A2-B5-C19; A2-B5-C20;A2-B5-C21; A2-B5-C22; A2-B5-C23; A2-B5-C24; A2-B5-C25; A2-B5-C26;A2-B5-C27; A2-B5-C28; A2-B5-C29; A2-B5-C30; A2-B5-C31; A2-B5-C32;A2-B5-C33; A2-B5-C34; A2-B5-C35; A2-B5-C36; A2-B5-C37; A2-B5-C38;A2-B5-C39; A2-B5-C40; A2-B5-C41; A2-B5-C42; A2-B5-C43; A2-B5-C44;A2-B5-C45; A2-B5-C46; A3-B5-C1; A3-B5-C2; A3-B5-C3; A3-B5-C4; A3-B5-C5;A3-B5-C6; A3-B5-C7; A3-B5-C8; A3-B5-C9; A3-B5-C10; A3-B5-C11; A3-B5-C12;A3-B5-C13; A3-B5-C14; A3-B5-C15; A3-B5-C16; A3-B5-C17; A3-B5-C18;A3-B5-C19; A3-B5-C20; A3-B5-C21; A3-B5-C22; A3-B5-C23; A3-B5-C24;A3-B5-C25; A3-B5-C26; A3-B5-C27; A3-B5-C28; A3-B5-C29; A3-B5-C30;A3-B5-C31; A3-B5-C32; A3-B5-C33; A3-B5-C34; A3-B5-C35; A3-B5-C36;A3-B5-C37; A3-B5-C38; A3-B5-C39; A3-B5-C40; A3-B5-C41; A3-B5-C42;A3-B5-C43; A3-B5-C44; A3-B5-C45; A3-B5-C46; A4-B5-C1; A4-B5-C2;A4-B5-C3; A4-B5-C4; A4-B5-C5; A4-B5-C6; A4-B5-C7; A4-B5-C8; A4-B5-C9;A4-B5-C10; A4-B5-C11; A4-B5-C12; A4-B5-C13; A4-B5-C14; A4-B5-C15;A4-B5-C16; A4-B5-C17; A4-B5-C18; A4-B5-C19; A4-B5-C20; A4-B5-C21;A4-B5-C22; A4-B5-C23; A4-B5-C24; A4-B5-C25; A4-B5-C26; A4-B5-C27;A4-B5-C28; A4-B5-C29; A4-B5-C30; A4-B5-C31; A4-B5-C32; A4-B5-C33;A4-B5-C34; A4-B5-C35; A4-B5-C36; A4-B5-C37; A4-B5-C38; A4-B5-C39;A4-B5-C40; A4-B5-C41; A4-B5-C42; A4-B5-C43; A4-B5-C44; A4-B5-C45;A4-B5-C46; A5-B5-C1; A5-B5-C2; A5-B5-C3; A5-B5-C4; A5-B5-C5; A5-B5-C6;A5-B5-C7; A5-B5-C8; A5-B5-C9; A5-B5-C10; A5-B5-C11; A5-B5-C12;A5-B5-C13; A5-B5-C14; A5-B5-C15; A5-B5-C16; A5-B5-C17; A5-B5-C18;A5-B5-C19; A5-B5-C20; A5-B5-C21; A5-B5-C22; A5-B5-C23; A5-B5-C24;A5-B5-C25; A5-B5-C26; A5-B5-C27; A5-B5-C28; A5-B5-C29; A5-B5-C30;A5-B5-C31; A5-B5-C32; A5-B5-C33; A5-B5-C34; A5-B5-C35; A5-B5-C36;A5-B5-C37; A5-B5-C38; A5-B5-C39; A5-B5-C40; A5-B5-C41; A5-B5-C42;A5-B5-C43; A5-B5-C44; A5-B5-C45; A5-B5-C46; A6-B5-C1; A6-B5-C2;A6-B5-C3; A6-B5-C4; A6-B5-C5; A6-B5-C6; A6-B5-C7; A6-B5-C8; A6-B5-C9;A6-B5-C10; A6-B5-C11; A6-B5-C12; A6-B5-C13; A6-B5-C14; A6-B5-C15;A6-B5-C16; A6-B5-C17; A6-B5-C18; A6-B5-C19; A6-B5-C20; A6-B5-C21;A6-B5-C22; A6-B5-C23; A6-B5-C24; A6-B5-C25; A6-B5-C26; A6-B5-C27;A6-B5-C28; A6-B5-C29; A6-B5-C30; A6-B5-C31; A6-B5-C32; A6-B5-C33;A6-B5-C34; A6-B5-C35; A6-B5-C36; A6-B5-C37; A6-B5-C38; A6-B5-C39;A6-B5-C40; A6-B5-C41; A6-B5-C42; A6-B5-C43; A6-B5-C44; A6-B5-C45;A6-B5-C46; A7-B5-C1; A7-B5-C2; A7-B5-C3; A7-B5-C4; A7-B5-C5; A7-B5-C6;A7-B5-C7; A7-B5-C8; A7-B5-C9; A7-B5-C10; A7-B5-C11; A7-B5-C12;A7-B5-C13; A7-B5-C14; A7-B5-C15; A7-B5-C16; A7-B5-C17; A7-B5-C18;A7-B5-C19; A7-B5-C20; A7-B5-C21; A7-B5-C22; A7-B5-C23; A7-B5-C24;A7-B5-C25; A7-B5-C26; A7-B5-C27; A7-B5-C28; A7-B5-C29; A7-B5-C30;A7-B5-C31; A7-B5-C32; A7-B5-C33; A7-B5-C34; A7-B5-C35; A7-B5-C36;A7-B5-C37; A7-B5-C38; A7-B5-C39; A7-B5-C40; A7-B5-C41; A7-B5-C42;A7-B5-C43; A7-B5-C44; A7-B5-C45; A7-B5-C46; A8-B5-C1; A8-B5-C2;A8-B5-C3; A8-B5-C4; A8-B5-C5; A8-B5-C6; A8-B5-C7; A8-B5-C8; A8-B5-C9;A8-B5-C10; A8-B5-C11; A8-B5-C12; A8-B5-C13; A8-B5-C14; A8-B5-C15;A8-B5-C16; A8-B5-C17; A8-B5-C18; A8-B5-C19; A8-B5-C20; A8-B5-C21;A8-B5-C22; A8-B5-C23; A8-B5-C24; A8-B5-C25; A8-B5-C26; A8-B5-C27;A8-B5-C28; A8-B5-C29; A8-B5-C30; A8-B5-C31; A8-B5-C32; A8-B5-C33;A8-B5-C34; A8-B5-C35; A8-B5-C36; A8-B5-C37; A8-B5-C38; A8-B5-C39;A8-B5-C40; A8-B5-C41; A8-B5-C42; A8-B5-C43; A8-B5-C44; A8-B5-C45;A8-B5-C46; A9-B5-C1; A9-B5-C2; A9-B5-C3; A9-B5-C4; A9-B5-C5; A9-B5-C6;A9-B5-C7; A9-B5-C8; A9-B5-C9; A9-B5-C10; A9-B5-C11; A9-B5-C12;A9-B5-C13; A9-B5-C14; A9-B5-C15; A9-B5-C16; A9-B5-C17; A9-B5-C18;A9-B5-C19; A9-B5-C20; A9-B5-C21; A9-B5-C22; A9-B5-C23; A9-B5-C24;A9-B5-C25; A9-B5-C26; A9-B5-C27; A9-B5-C28; A9-B5-C29; A9-B5-C30;A9-B5-C31; A9-B5-C32; A9-B5-C33; A9-B5-C34; A9-B5-C35; A9-B5-C36;A9-B5-C37; A9-B5-C38; A9-B5-C39; A9-B5-C40; A9-B5-C41; A9-B5-C42;A9-B5-C43; A9-B5-C44; A9-B5-C45; A9-B5-C46; A10-B5-C1; A10-B5-C2;A10-B5-C3; A10-B5-C4; A10-B5-C5; A10-B5-C6; A10-B5-C7; A10-B5-C8;A10-B5-C9; A10-B5-C10; A10-B5-C11; A10-B5-C12; A10-B5-C13; A10-B5-C14;A10-B5-C15; A10-B5-C16; A10-B5-C17; A10-B5-C18; A10-B5-C19; A10-B5-C20;A10-B5-C21; A10-B5-C22; A10-B5-C23; A10-B5-C24; A10-B5-C25; A10-B5-C26;A10-B5-C27; A10-B5-C28; A10-B5-C29; A10-B5-C30; A10-B5-C31; A10-B5-C32;A10-B5-C33; A10-B5-C34; A10-B5-C35; A10-B5-C36; A10-B5-C37; A10-B5-C38;A10-B5-C39; A10-B5-C40; A10-B5-C41; A10-B5-C42; A10-B5-C43; A10-B5-C44;A10-B5-C45; A10-B5-C46; A11-B5-C1; A11-B5-C2; A11-B5-C3; A11-B5-C4;A11-B5-C5; A11-B5-C6; A11-B5-C7; A11-B5-C8; A11-B5-C9; A11-B5-C10;A11-B5-C11; A11-B5-C12; A11-B5-C13; A11-B5-C14; A11-B5-C15; A11-B5-C16;A11-B5-C17; A11-B5-C18; A11-B5-C19; A11-B5-C20; A11-B5-C21; A11-B5-C22;A11-B5-C23; A11-B5-C24; A11-B5-C25; A11-B5-C26; A11-B5-C27; A11-B5-C28;A11-B5-C29; A11-B5-C30; A11-B5-C31; A11-B5-C32; A11-B5-C33; A11-B5-C34;A11-B5-C35; A11-B5-C36; A11-B5-C37; A11-B5-C38; A11-B5-C39; A11-B5-C40;A11-B5-C41; A11-B5-C42; A11-B5-C43; A11-B5-C44; A11-B5-C45; A11-B5-C46;A12-B5-C1; A12-B5-C2; A12-B5-C3; A12-B5-C4; A12-B5-C5; A12-B5-C6;A12-B5-C7; A12-B5-C8; A12-B5-C9; A12-B5-C10; A12-B5-C11; A12-B5-C12;A12-B5-C13; A12-B5-C14; A12-B5-C15; A12-B5-C16; A12-B5-C17; A12-B5-C18;A12-B5-C19; A12-B5-C20; A12-B5-C21; A12-B5-C22; A12-B5-C23; A12-B5-C24;A12-B5-C25; A12-B5-C26; A12-B5-C27; A12-B5-C28; A12-B5-C29; A12-B5-C30;A12-B5-C31; A12-B5-C32; A12-B5-C33; A12-B5-C34; A12-B5-C35; A12-B5-C36;A12-B5-C37; A12-B5-C38; A12-B5-C39; A12-B5-C40; A12-B5-C41; A12-B5-C42;A12-B5-C43; A12-B5-C44; A12-B5-C45; A12-B5-C46; A13-B5-C1; A13-B5-C2;A13-B5-C3; A13-B5-C4; A13-B5-C5; A13-B5-C6; A13-B5-C7; A13-B5-C8;A13-B5-C9; A13-B5-C10; A13-B5-C11; A13-B5-C12; A13-B5-C13; A13-B5-C14;A13-B5-C15; A13-B5-C16; A13-B5-C17; A13-B5-C18; A13-B5-C19; A13-B5-C20;A13-B5-C21; A13-B5-C22; A13-B5-C23; A13-B5-C24; A13-B5-C25; A13-B5-C26;A13-B5-C27; A13-B5-C28; A13-B5-C29; A13-B5-C30; A13-B5-C31; A13-B5-C32;A13-B5-C33; A13-B5-C34; A13-B5-C35; A13-B5-C36; A13-B5-C37; A13-B5-C38;A13-B5-C39; A13-B5-C40; A13-B5-C41; A13-B5-C42; A13-B5-C43; A13-B5-C44;A13-B5-C45; A13-B5-C46; A14-B5-C1; A14-B5-C2; A14-B5-C3; A14-B5-C4;A14-B5-C5; A14-B5-C6; A14-B5-C7; A14-B5-C8; A14-B5-C9; A14-B5-C10;A14-B5-C11; A14-B5-C12; A14-B5-C13; A14-B5-C14; A14-B5-C15; A14-B5-C16;A14-B5-C17; A14-B5-C18; A14-B5-C19; A14-B5-C20; A14-B5-C21; A14-B5-C22;A14-B5-C23; A14-B5-C24; A14-B5-C25; A14-B5-C26; A14-B5-C27; A14-B5-C28;A14-B5-C29; A14-B5-C30; A14-B5-C31; A14-B5-C32; A14-B5-C33; A14-B5-C34;A14-B5-C35; A14-B5-C36; A14-B5-C37; A14-B5-C38; A14-B5-C39; A14-B5-C40;A14-B5-C41; A14-B5-C42; A14-B5-C43; A14-B5-C44; A14-B5-C45; A14-B5-C46;A15-B5-C1; A15-B5-C2; A15-B5-C3; A15-B5-C4; A15-B5-C5; A15-B5-C6;A15-B5-C7; A15-B5-C8; A15-B5-C9; A15-B5-C10; A15-B5-C11; A15-B5-C12;A15-B5-C13; A15-B5-C14; A15-B5-C15; A15-B5-C16; A15-B5-C17; A15-B5-C18;A15-B5-C19; A15-B5-C20; A15-B5-C21; A15-B5-C22; A15-B5-C23; A15-B5-C24;A15-B5-C25; A15-B5-C26; A15-B5-C27; A15-B5-C28; A15-B5-C29; A15-B5-C30;A15-B5-C31; A15-B5-C32; A15-B5-C33; A15-B5-C34; A15-B5-C35; A15-B5-C36;A15-B5-C37; A15-B5-C38; A15-B5-C39; A15-B5-C40; A15-B5-C41; A15-B5-C42;A15-B5-C43; A15-B5-C44; A15-B5-C45; A15-B5-C46; A16-B5-C1; A16-B5-C2;A16-B5-C3; A16-B5-C4; A16-B5-C5; A16-B5-C6; A16-B5-C7; A16-B5-C8;A16-B5-C9; A16-B5-C10; A16-B5-C11; A16-B5-C12; A16-B5-C13; A16-B5-C14;A16-B5-C15; A16-B5-C16; A16-B5-C17; A16-B5-C18; A16-B5-C19; A16-B5-C20;A16-B5-C21; A16-B5-C22; A16-B5-C23; A16-B5-C24; A16-B5-C25; A16-B5-C26;A16-B5-C27; A16-B5-C28; A16-B5-C29; A16-B5-C30; A16-B5-C31; A16-B5-C32;A16-B5-C33; A16-B5-C34; A16-B5-C35; A16-B5-C36; A16-B5-C37; A16-B5-C38;A16-B5-C39; A16-B5-C40; A16-B5-C41; A16-B5-C42; A16-B5-C43; A16-B5-C44;A16-B5-C45; A16-B5-C46; A17-B5-C1; A17-B5-C2; A17-B5-C3; A17-B5-C4;A17-B5-C5; A17-B5-C6; A17-B5-C7; A17-B5-C8; A17-B5-C9; A17-B5-C10;A17-B5-C11; A17-B5-C12; A17-B5-C13; A17-B5-C14; A17-B5-C15; A17-B5-C16;A17-B5-C17; A17-B5-C18; A17-B5-C19; A17-B5-C20; A17-B5-C21; A17-B5-C22;A17-B5-C23; A17-B5-C24; A17-B5-C25; A17-B5-C26; A17-B5-C27; A17-B5-C28;A17-B5-C29; A17-B5-C30; A17-B5-C31; A17-B5-C32; A17-B5-C33; A17-B5-C34;A17-B5-C35; A17-B5-C36; A17-B5-C37; A17-B5-C38; A17-B5-C39; A17-B5-C40;A17-B5-C41; A17-B5-C42; A17-B5-C43; A17-B5-C44; A17-B5-C45; A17-B5-C46;A18-B5-C1; A18-B5-C2; A18-B5-C3; A18-B5-C4; A18-B5-C5; A18-B5-C6;A18-B5-C7; A18-B5-C8; A18-B5-C9; A18-B5-C10; A18-B5-C11; A18-B5-C12;A18-B5-C13; A18-B5-C14; A18-B5-C15; A18-B5-C16; A18-B5-C17; A18-B5-C18;A18-B5-C19; A18-B5-C20; A18-B5-C21; A18-B5-C22; A18-B5-C23; A18-B5-C24;A18-B5-C25; A18-B5-C26; A18-B5-C27; A18-B5-C28; A18-B5-C29; A18-B5-C30;A18-B5-C31; A18-B5-C32; A18-B5-C33; A18-B5-C34; A18-B5-C35; A18-B5-C36;A18-B5-C37; A18-B5-C38; A18-B5-C39; A18-B5-C40; A18-B5-C41; A18-B5-C42;A18-B5-C43; A18-B5-C44; A18-B5-C45; A18-B5-C46; A19-B5-C1; A19-B5-C2;A19-B5-C3; A19-B5-C4; A19-B5-C5; A19-B5-C6; A19-B5-C7; A19-B5-C8;A19-B5-C9; A19-B5-C10; A19-B5-C11; A19-B5-C12; A19-B5-C13; A19-B5-C14;A19-B5-C15; A19-B5-C16; A19-B5-C17; A19-B5-C18; A19-B5-C19; A19-B5-C20;A19-B5-C21; A19-B5-C22; A19-B5-C23; A19-B5-C24; A19-B5-C25; A19-B5-C26;A19-B5-C27; A19-B5-C28; A19-B5-C29; A19-B5-C30; A19-B5-C31; A19-B5-C32;A19-B5-C33; A19-B5-C34; A19-B5-C35; A19-B5-C36; A19-B5-C37; A19-B5-C38;A19-B5-C39; A19-B5-C40; A19-B5-C41; A19-B5-C42; A19-B5-C43; A19-B5-C44;A19-B5-C45; A19-B5-C46; A20-B5-C1; A20-B5-C2; A20-B5-C3; A20-B5-C4;A20-B5-C5; A20-B5-C6; A20-B5-C7; A20-B5-C8; A20-B5-C9; A20-B5-C10;A20-B5-C11; A20-B5-C12; A20-B5-C13; A20-B5-C14; A20-B5-C15; A20-B5-C16;A20-B5-C17; A20-B5-C18; A20-B5-C19; A20-B5-C20; A20-B5-C21; A20-B5-C22;A20-B5-C23; A20-B5-C24; A20-B5-C25; A20-B5-C26; A20-B5-C27; A20-B5-C28;A20-B5-C29; A20-B5-C30; A20-B5-C31; A20-B5-C32; A20-B5-C33; A20-B5-C34;A20-B5-C35; A20-B5-C36; A20-B5-C37; A20-B5-C38; A20-B5-C39; A20-B5-C40;A20-B5-C41; A20-B5-C42; A20-B5-C43; A20-B5-C44; A20-B5-C45; A20-B5-C46;A21-B5-C1; A21-B5-C2; A21-B5-C3; A21-B5-C4; A21-B5-C5; A21-B5-C6;A21-B5-C7; A21-B5-C8; A21-B5-C9; A21-B5-C10; A21-B5-C11; A21-B5-C12;A21-B5-C13; A21-B5-C14; A21-B5-C15; A21-B5-C16; A21-B5-C17; A21-B5-C18;A21-B5-C19; A21-B5-C20; A21-B5-C21; A21-B5-C22; A21-B5-C23; A21-B5-C24;A21-B5-C25; A21-B5-C26; A21-B5-C27; A21-B5-C28; A21-B5-C29; A21-B5-C30;A21-B5-C31; A21-B5-C32; A21-B5-C33; A21-B5-C34; A21-B5-C35; A21-B5-C36;A21-B5-C37; A21-B5-C38; A21-B5-C39; A21-B5-C40; A21-B5-C41; A21-B5-C42;A21-B5-C43; A21-B5-C44; A21-B5-C45; A21-B5-C46; A22-B5-C1; A22-B5-C2;A22-B5-C3; A22-B5-C4; A22-B5-C5; A22-B5-C6; A22-B5-C7; A22-B5-C8;A22-B5-C9; A22-B5-C10; A22-B5-C11; A22-B5-C12; A22-B5-C13; A22-B5-C14;A22-B5-C15; A22-B5-C16; A22-B5-C17; A22-B5-C18; A22-B5-C19; A22-B5-C20;A22-B5-C21; A22-B5-C22; A22-B5-C23; A22-B5-C24; A22-B5-C25; A22-B5-C26;A22-B5-C27; A22-B5-C28; A22-B5-C29; A22-B5-C30; A22-B5-C31; A22-B5-C32;A22-B5-C33; A22-B5-C34; A22-B5-C35; A22-B5-C36; A22-B5-C37; A22-B5-C38;A22-B5-C39; A22-B5-C40; A22-B5-C41; A22-B5-C42; A22-B5-C43; A22-B5-C44;A22-B5-C45; A22-B5-C46; A23-B5-C1; A23-B5-C2; A23-B5-C3; A23-B5-C4;A23-B5-C5; A23-B5-C6; A23-B5-C7; A23-B5-C8; A23-B5-C9; A23-B5-C10;A23-B5-C11; A23-B5-C12; A23-B5-C13; A23-B5-C14; A23-B5-C15; A23-B5-C16;A23-B5-C17; A23-B5-C18; A23-B5-C19; A23-B5-C20; A23-B5-C21; A23-B5-C22;A23-B5-C23; A23-B5-C24; A23-B5-C25; A23-B5-C26; A23-B5-C27; A23-B5-C28;A23-B5-C29; A23-B5-C30; A23-B5-C31; A23-B5-C32; A23-B5-C33; A23-B5-C34;A23-B5-C35; A23-B5-C36; A23-B5-C37; A23-B5-C38; A23-B5-C39; A23-B5-C40;A23-B5-C41; A23-B5-C42; A23-B5-C43; A23-B5-C44; A23-B5-C45; A23-B5-C46;A24-B5-C1; A24-B5-C2; A24-B5-C3; A24-B5-C4; A24-B5-C5; A24-B5-C6;A24-B5-C7; A24-B5-C8; A24-B5-C9; A24-B5-C10; A24-B5-C11; A24-B5-C12;A24-B5-C13; A24-B5-C14; A24-B5-C15; A24-B5-C16; A24-B5-C17; A24-B5-C18;A24-B5-C19; A24-B5-C20; A24-B5-C21; A24-B5-C22; A24-B5-C23; A24-B5-C24;A24-B5-C25; A24-B5-C26; A24-B5-C27; A24-B5-C28; A24-B5-C29; A24-B5-C30;A24-B5-C31; A24-B5-C32; A24-B5-C33; A24-B5-C34; A24-B5-C35; A24-B5-C36;A24-B5-C37; A24-B5-C38; A24-B5-C39; A24-B5-C40; A24-B5-C41; A24-B5-C42;A24-B5-C43; A24-B5-C44; A24-B5-C45; A24-B5-C46; A25-B5-C1; A25-B5-C2;A25-B5-C3; A25-B5-C4; A25-B5-C5; A25-B5-C6; A25-B5-C7; A25-B5-C8;A25-B5-C9; A25-B5-C10; A25-B5-C11; A25-B5-C12; A25-B5-C13; A25-B5-C14;A25-B5-C15; A25-B5-C16; A25-B5-C17; A25-B5-C18; A25-B5-C19; A25-B5-C20;A25-B5-C21; A25-B5-C22; A25-B5-C23; A25-B5-C24; A25-B5-C25; A25-B5-C26;A25-B5-C27; A25-B5-C28; A25-B5-C29; A25-B5-C30; A25-B5-C31; A25-B5-C32;A25-B5-C33; A25-B5-C34; A25-B5-C35; A25-B5-C36; A25-B5-C37; A25-B5-C38;A25-B5-C39; A25-B5-C40; A25-B5-C41; A25-B5-C42; A25-B5-C43; A25-B5-C44;A25-B5-C45; A25-B5-C46; A26-B5-C1; A26-B5-C2; A26-B5-C3; A26-B5-C4;A26-B5-C5; A26-B5-C6; A26-B5-C7; A26-B5-C8; A26-B5-C9; A26-B5-C10;A26-B5-C11; A26-B5-C12; A26-B5-C13; A26-B5-C14; A26-B5-C15; A26-B5-C16;A26-B5-C17; A26-B5-C18; A26-B5-C19; A26-B5-C20; A26-B5-C21; A26-B5-C22;A26-B5-C23; A26-B5-C24; A26-B5-C25; A26-B5-C26; A26-B5-C27; A26-B5-C28;A26-B5-C29; A26-B5-C30; A26-B5-C31; A26-B5-C32; A26-B5-C33; A26-B5-C34;A26-B5-C35; A26-B5-C36; A26-B5-C37; A26-B5-C38; A26-B5-C39; A26-B5-C40;A26-B5-C41; A26-B5-C42; A26-B5-C43; A26-B5-C44; A26-B5-C45; A26-B5-C46;A27-B5-C1; A27-B5-C2; A27-B5-C3; A27-B5-C4; A27-B5-C5; A27-B5-C6;A27-B5-C7; A27-B5-C8; A27-B5-C9; A27-B5-C10; A27-B5-C11; A27-B5-C12;A27-B5-C13; A27-B5-C14; A27-B5-C15; A27-B5-C16; A27-B5-C17; A27-B5-C18;A27-B5-C19; A27-B5-C20; A27-B5-C21; A27-B5-C22; A27-B5-C23; A27-B5-C24;A27-B5-C25; A27-B5-C26; A27-B5-C27; A27-B5-C28; A27-B5-C29; A27-B5-C30;A27-B5-C31; A27-B5-C32; A27-B5-C33; A27-B5-C34; A27-B5-C35; A27-B5-C36;A27-B5-C37; A27-B5-C38; A27-B5-C39; A27-B5-C40; A27-B5-C41; A27-B5-C42;A27-B5-C43; A27-B5-C44; A27-B5-C45; A27-B5-C46; A28-B5-C1; A28-B5-C2;A28-B5-C3; A28-B5-C4; A28-B5-C5; A28-B5-C6; A28-B5-C7; A28-B5-C8;A28-B5-C9; A28-B5-C10; A28-B5-C11; A28-B5-C12; A28-B5-C13; A28-B5-C14;A28-B5-C15; A28-B5-C16; A28-B5-C17; A28-B5-C18; A28-B5-C19; A28-B5-C20;A28-B5-C21; A28-B5-C22; A28-B5-C23; A28-B5-C24; A28-B5-C25; A28-B5-C26;A28-B5-C27; A28-B5-C28; A28-B5-C29; A28-B5-C30; A28-B5-C31; A28-B5-C32;A28-B5-C33; A28-B5-C34; A28-B5-C35; A28-B5-C36; A28-B5-C37; A28-B5-C38;A28-B5-C39; A28-B5-C40; A28-B5-C41; A28-B5-C42; A28-B5-C43; A28-B5-C44;A28-B5-C45; A28-B5-C46; A1-B6-C1; A1-B6-C2; A1-B6-C3; A1-B6-C4;A1-B6-C5; A1-B6-C6; A1-B6-C7; A1-B6-C8; A1-B6-C9; A1-B6-C10; A1-B6-C11;A1-B6-C12; A1-B6-C13; A1-B6-C14; A1-B6-C15; A1-B6-C16; A1-B6-C17;A1-B6-C18; A1-B6-C19; A1-B6-C20; A1-B6-C21; A1-B6-C22; A1-B6-C23;A1-B6-C24; A1-B6-C25; A1-B6-C26; A1-B6-C27; A1-B6-C28; A1-B6-C29;A1-B6-C30; A1-B6-C31; A1-B6-C32; A1-B6-C33; A1-B6-C34; A1-B6-C35;A1-B6-C36; A1-B6-C37; A1-B6-C38; A1-B6-C39; A1-B6-C40; A1-B6-C41;A1-B6-C42; A1-B6-C43; A1-B6-C44; A1-B6-C45; A1-B6-C46; A2-B6-C1;A2-B6-C2; A2-B6-C3; A2-B6-C4; A2-B6-C5; A2-B6-C6; A2-B6-C7; A2-B6-C8;A2-B6-C9; A2-B6-C10; A2-B6-C11; A2-B6-C12; A2-B6-C13; A2-B6-C14;A2-B6-C15; A2-B6-C16; A2-B6-C17; A2-B6-C18; A2-B6-C19; A2-B6-C20;A2-B6-C21; A2-B6-C22; A2-B6-C23; A2-B6-C24; A2-B6-C25; A2-B6-C26;A2-B6-C27; A2-B6-C28; A2-B6-C29; A2-B6-C30; A2-B6-C31; A2-B6-C32;A2-B6-C33; A2-B6-C34; A2-B6-C35; A2-B6-C36; A2-B6-C37; A2-B6-C38;A2-B6-C39; A2-B6-C40; A2-B6-C41; A2-B6-C42; A2-B6-C43; A2-B6-C44;A2-B6-C45; A2-B6-C46; A3-B6-C1; A3-B6-C2; A3-B6-C3; A3-B6-C4; A3-B6-C5;A3-B6-C6; A3-B6-C7; A3-B6-C8; A3-B6-C9; A3-B6-C10; A3-B6-C11; A3-B6-C12;A3-B6-C13; A3-B6-C14; A3-B6-C15; A3-B6-C16; A3-B6-C17; A3-B6-C18;A3-B6-C19; A3-B6-C20; A3-B6-C21; A3-B6-C22; A3-B6-C23; A3-B6-C24;A3-B6-C25; A3-B6-C26; A3-B6-C27; A3-B6-C28; A3-B6-C29; A3-B6-C30;A3-B6-C31; A3-B6-C32; A3-B6-C33; A3-B6-C34; A3-B6-C35; A3-B6-C36;A3-B6-C37; A3-B6-C38; A3-B6-C39; A3-B6-C40; A3-B6-C41; A3-B6-C42;A3-B6-C43; A3-B6-C44; A3-B6-C45; A3-B6-C46; A4-B6-C1; A4-B6-C2;A4-B6-C3; A4-B6-C4; A4-B6-C5; A4-B6-C6; A4-B6-C7; A4-B6-C8; A4-B6-C9;A4-B6-C10; A4-B6-C11; A4-B6-C12; A4-B6-C13; A4-B6-C14; A4-B6-C15;A4-B6-C16; A4-B6-C17; A4-B6-C18; A4-B6-C19; A4-B6-C20; A4-B6-C21;A4-B6-C22; A4-B6-C23; A4-B6-C24; A4-B6-C25; A4-B6-C26; A4-B6-C27;A4-B6-C28; A4-B6-C29; A4-B6-C30; A4-B6-C31; A4-B6-C32; A4-B6-C33;A4-B6-C34; A4-B6-C35; A4-B6-C36; A4-B6-C37; A4-B6-C38; A4-B6-C39;A4-B6-C40; A4-B6-C41; A4-B6-C42; A4-B6-C43; A4-B6-C44; A4-B6-C45;A4-B6-C46; A5-B6-C1; A5-B6-C2; A5-B6-C3; A5-B6-C4; A5-B6-C5; A5-B6-C6;A5-B6-C7; A5-B6-C8; A5-B6-C9; A5-B6-C10; A5-B6-C11; A5-B6-C12;A5-B6-C13; A5-B6-C14; A5-B6-C15; A5-B6-C16; A5-B6-C17; A5-B6-C18;A5-B6-C19; A5-B6-C20; A5-B6-C21; A5-B6-C22; A5-B6-C23; A5-B6-C24;A5-B6-C25; A5-B6-C26; A5-B6-C27; A5-B6-C28; A5-B6-C29; A5-B6-C30;A5-B6-C31; A5-B6-C32; A5-B6-C33; A5-B6-C34; A5-B6-C35; A5-B6-C36;A5-B6-C37; A5-B6-C38; A5-B6-C39; A5-B6-C40; A5-B6-C41; A5-B6-C42;A5-B6-C43; A5-B6-C44; A5-B6-C45; A5-B6-C46; A6-B6-C1; A6-B6-C2;A6-B6-C3; A6-B6-C4; A6-B6-C5; A6-B6-C6; A6-B6-C7; A6-B6-C8; A6-B6-C9;A6-B6-C10; A6-B6-C11; A6-B6-C12; A6-B6-C13; A6-B6-C14; A6-B6-C15;A6-B6-C16; A6-B6-C17; A6-B6-C18; A6-B6-C19; A6-B6-C20; A6-B6-C21;A6-B6-C22; A6-B6-C23; A6-B6-C24; A6-B6-C25; A6-B6-C26; A6-B6-C27;A6-B6-C28; A6-B6-C29; A6-B6-C30; A6-B6-C31; A6-B6-C32; A6-B6-C33;A6-B6-C34; A6-B6-C35; A6-B6-C36; A6-B6-C37; A6-B6-C38; A6-B6-C39;A6-B6-C40; A6-B6-C41; A6-B6-C42; A6-B6-C43; A6-B6-C44; A6-B6-C45;A6-B6-C46; A7-B6-C1; A7-B6-C2; A7-B6-C3; A7-B6-C4; A7-B6-C5; A7-B6-C6;A7-B6-C7; A7-B6-C8; A7-B6-C9; A7-B6-C10; A7-B6-C11; A7-B6-C12;A7-B6-C13; A7-B6-C14; A7-B6-C15; A7-B6-C16; A7-B6-C17; A7-B6-C18;A7-B6-C19; A7-B6-C20; A7-B6-C21; A7-B6-C22; A7-B6-C23; A7-B6-C24;A7-B6-C25; A7-B6-C26; A7-B6-C27; A7-B6-C28; A7-B6-C29; A7-B6-C30;A7-B6-C31; A7-B6-C32; A7-B6-C33; A7-B6-C34; A7-B6-C35; A7-B6-C36;A7-B6-C37; A7-B6-C38; A7-B6-C39; A7-B6-C40; A7-B6-C41; A7-B6-C42;A7-B6-C43; A7-B6-C44; A7-B6-C45; A7-B6-C46; A8-B6-C1; A8-B6-C2;A8-B6-C3; A8-B6-C4; A8-B6-C5; A8-B6-C6; A8-B6-C7; A8-B6-C8; A8-B6-C9;A8-B6-C10; A8-B6-C11; A8-B6-C12; A8-B6-C13; A8-B6-C14; A8-B6-C15;A8-B6-C16; A8-B6-C17; A8-B6-C18; A8-B6-C19; A8-B6-C20; A8-B6-C21;A8-B6-C22; A8-B6-C23; A8-B6-C24; A8-B6-C25; A8-B6-C26; A8-B6-C27;A8-B6-C28; A8-B6-C29; A8-B6-C30; A8-B6-C31; A8-B6-C32; A8-B6-C33;A8-B6-C34; A8-B6-C35; A8-B6-C36; A8-B6-C37; A8-B6-C38; A8-B6-C39;A8-B6-C40; A8-B6-C41; A8-B6-C42; A8-B6-C43; A8-B6-C44; A8-B6-C45;A8-B6-C46; A9-B6-C1; A9-B6-C2; A9-B6-C3; A9-B6-C4; A9-B6-C5; A9-B6-C6;A9-B6-C7; A9-B6-C8; A9-B6-C9; A9-B6-C10; A9-B6-C11; A9-B6-C12;A9-B6-C13; A9-B6-C14; A9-B6-C15; A9-B6-C16; A9-B6-C17; A9-B6-C18;A9-B6-C19; A9-B6-C20; A9-B6-C21; A9-B6-C22; A9-B6-C23; A9-B6-C24;A9-B6-C25; A9-B6-C26; A9-B6-C27; A9-B6-C28; A9-B6-C29; A9-B6-C30;A9-B6-C31; A9-B6-C32; A9-B6-C33; A9-B6-C34; A9-B6-C35; A9-B6-C36;A9-B6-C37; A9-B6-C38; A9-B6-C39; A9-B6-C40; A9-B6-C41; A9-B6-C42;A9-B6-C43; A9-B6-C44; A9-B6-C45; A9-B6-C46; A10-B6-C1; A10-B6-C2;A10-B6-C3; A10-B6-C4; A10-B6-C5; A10-B6-C6; A10-B6-C7; A10-B6-C8;A10-B6-C9; A10-B6-C10; A10-B6-C11; A10-B6-C12; A10-B6-C13; A10-B6-C14;A10-B6-C15; A10-B6-C16; A10-B6-C17; A10-B6-C18; A10-B6-C19; A10-B6-C20;A10-B6-C21; A10-B6-C22; A10-B6-C23; A10-B6-C24; A10-B6-C25; A10-B6-C26;A10-B6-C27; A10-B6-C28; A10-B6-C29; A10-B6-C30; A10-B6-C31; A10-B6-C32;A10-B6-C33; A10-B6-C34; A10-B6-C35; A10-B6-C36; A10-B6-C37; A10-B6-C38;A10-B6-C39; A10-B6-C40; A10-B6-C41; A10-B6-C42; A10-B6-C43; A10-B6-C44;A10-B6-C45; A10-B6-C46; A11-B6-C1; A11-B6-C2; A11-B6-C3; A11-B6-C4;A11-B6-C5; A11-B6-C6; A11-B6-C7; A11-B6-C8; A11-B6-C9; A11-B6-C10;A11-B6-C11; A11-B6-C12; A11-B6-C13; A11-B6-C14; A11-B6-C15; A11-B6-C16;A11-B6-C17; A11-B6-C18; A11-B6-C19; A11-B6-C20; A11-B6-C21; A11-B6-C22;A11-B6-C23; A11-B6-C24; A11-B6-C25; A11-B6-C26; A11-B6-C27; A11-B6-C28;A11-B6-C29; A11-B6-C30; A11-B6-C31; A11-B6-C32; A11-B6-C33; A11-B6-C34;A11-B6-C35; A11-B6-C36; A11-B6-C37; A11-B6-C38; A11-B6-C39; A11-B6-C40;A11-B6-C41; A11-B6-C42; A11-B6-C43; A11-B6-C44; A11-B6-C45; A11-B6-C46;A12-B6-C1; A12-B6-C2; A12-B6-C3; A12-B6-C4; A12-B6-C5; A12-B6-C6;A12-B6-C7; A12-B6-C8; A12-B6-C9; A12-B6-C10; A12-B6-C11; A12-B6-C12;A12-B6-C13; A12-B6-C14; A12-B6-C15; A12-B6-C16; A12-B6-C17; A12-B6-C18;A12-B6-C19; A12-B6-C20; A12-B6-C21; A12-B6-C22; A12-B6-C23; A12-B6-C24;A12-B6-C25; A12-B6-C26; A12-B6-C27; A12-B6-C28; A12-B6-C29; A12-B6-C30;A12-B6-C31; A12-B6-C32; A12-B6-C33; A12-B6-C34; A12-B6-C35; A12-B6-C36;A12-B6-C37; A12-B6-C38; A12-B6-C39; A12-B6-C40; A12-B6-C41; A12-B6-C42;A12-B6-C43; A12-B6-C44; A12-B6-C45; A12-B6-C46; A13-B6-C1; A13-B6-C2;A13-B6-C3; A13-B6-C4; A13-B6-C5; A13-B6-C6; A13-B6-C7; A13-B6-C8;A13-B6-C9; A13-B6-C10; A13-B6-C11; A13-B6-C12; A13-B6-C13; A13-B6-C14;A13-B6-C15; A13-B6-C16; A13-B6-C17; A13-B6-C18; A13-B6-C19; A13-B6-C20;A13-B6-C21; A13-B6-C22; A13-B6-C23; A13-B6-C24; A13-B6-C25; A13-B6-C26;A13-B6-C27; A13-B6-C28; A13-B6-C29; A13-B6-C30; A13-B6-C31; A13-B6-C32;A13-B6-C33; A13-B6-C34; A13-B6-C35; A13-B6-C36; A13-B6-C37; A13-B6-C38;A13-B6-C39; A13-B6-C40; A13-B6-C41; A13-B6-C42; A13-B6-C43; A13-B6-C44;A13-B6-C45; A13-B6-C46; A14-B6-C1; A14-B6-C2; A14-B6-C3; A14-B6-C4;A14-B6-C5; A14-B6-C6; A14-B6-C7; A14-B6-C8; A14-B6-C9; A14-B6-C10;A14-B6-C11; A14-B6-C12; A14-B6-C13; A14-B6-C14; A14-B6-C15; A14-B6-C16;A14-B6-C17; A14-B6-C18; A14-B6-C19; A14-B6-C20; A14-B6-C21; A14-B6-C22;A14-B6-C23; A14-B6-C24; A14-B6-C25; A14-B6-C26; A14-B6-C27; A14-B6-C28;A14-B6-C29; A14-B6-C30; A14-B6-C31; A14-B6-C32; A14-B6-C33; A14-B6-C34;A14-B6-C35; A14-B6-C36; A14-B6-C37; A14-B6-C38; A14-B6-C39; A14-B6-C40;A14-B6-C41; A14-B6-C42; A14-B6-C43; A14-B6-C44; A14-B6-C45; A14-B6-C46;A15-B6-C1; A15-B6-C2; A15-B6-C3; A15-B6-C4; A15-B6-C5; A15-B6-C6;A15-B6-C7; A15-B6-C8; A15-B6-C9; A15-B6-C10; A15-B6-C11; A15-B6-C12;A15-B6-C13; A15-B6-C14; A15-B6-C15; A15-B6-C16; A15-B6-C17; A15-B6-C18;A15-B6-C19; A15-B6-C20; A15-B6-C21; A15-B6-C22; A15-B6-C23; A15-B6-C24;A15-B6-C25; A15-B6-C26; A15-B6-C27; A15-B6-C28; A15-B6-C29; A15-B6-C30;A15-B6-C31; A15-B6-C32; A15-B6-C33; A15-B6-C34; A15-B6-C35; A15-B6-C36;A15-B6-C37; A15-B6-C38; A15-B6-C39; A15-B6-C40; A15-B6-C41; A15-B6-C42;A15-B6-C43; A15-B6-C44; A15-B6-C45; A15-B6-C46; A16-B6-C1; A16-B6-C2;A16-B6-C3; A16-B6-C4; A16-B6-C5; A16-B6-C6; A16-B6-C7; A16-B6-C8;A16-B6-C9; A16-B6-C10; A16-B6-C11; A16-B6-C12; A16-B6-C13; A16-B6-C14;A16-B6-C15; A16-B6-C16; A16-B6-C17; A16-B6-C18; A16-B6-C19; A16-B6-C20;A16-B6-C21; A16-B6-C22; A16-B6-C23; A16-B6-C24; A16-B6-C25; A16-B6-C26;A16-B6-C27; A16-B6-C28; A16-B6-C29; A16-B6-C30; A16-B6-C31; A16-B6-C32;A16-B6-C33; A16-B6-C34; A16-B6-C35; A16-B6-C36; A16-B6-C37; A16-B6-C38;A16-B6-C39; A16-B6-C40; A16-B6-C41; A16-B6-C42; A16-B6-C43; A16-B6-C44;A16-B6-C45; A16-B6-C46; A17-B6-C1; A17-B6-C2; A17-B6-C3; A17-B6-C4;A17-B6-C5; A17-B6-C6; A17-B6-C7; A17-B6-C8; A17-B6-C9; A17-B6-C10;A17-B6-C11; A17-B6-C12; A17-B6-C13; A17-B6-C14; A17-B6-C15; A17-B6-C16;A17-B6-C17; A17-B6-C18; A17-B6-C19; A17-B6-C20; A17-B6-C21; A17-B6-C22;A17-B6-C23; A17-B6-C24; A17-B6-C25; A17-B6-C26; A17-B6-C27; A17-B6-C28;A17-B6-C29; A17-B6-C30; A17-B6-C31; A17-B6-C32; A17-B6-C33; A17-B6-C34;A17-B6-C35; A17-B6-C36; A17-B6-C37; A17-B6-C38; A17-B6-C39; A17-B6-C40;A17-B6-C41; A17-B6-C42; A17-B6-C43; A17-B6-C44; A17-B6-C45; A17-B6-C46;A18-B6-C1; A18-B6-C2; A18-B6-C3; A18-B6-C4; A18-B6-C5; A18-B6-C6;A18-B6-C7; A18-B6-C8; A18-B6-C9; A18-B6-C10; A18-B6-C11; A18-B6-C12;A18-B6-C13; A18-B6-C14; A18-B6-C15; A18-B6-C16; A18-B6-C17; A18-B6-C18;A18-B6-C19; A18-B6-C20; A18-B6-C21; A18-B6-C22; A18-B6-C23; A18-B6-C24;A18-B6-C25; A18-B6-C26; A18-B6-C27; A18-B6-C28; A18-B6-C29; A18-B6-C30;A18-B6-C31; A18-B6-C32; A18-B6-C33; A18-B6-C34; A18-B6-C35; A18-B6-C36;A18-B6-C37; A18-B6-C38; A18-B6-C39; A18-B6-C40; A18-B6-C41; A18-B6-C42;A18-B6-C43; A18-B6-C44; A18-B6-C45; A18-B6-C46; A19-B6-C1; A19-B6-C2;A19-B6-C3; A19-B6-C4; A19-B6-C5; A19-B6-C6; A19-B6-C7; A19-B6-C8;A19-B6-C9; A19-B6-C10; A19-B6-C11; A19-B6-C12; A19-B6-C13; A19-B6-C14;A19-B6-C15; A19-B6-C16; A19-B6-C17; A19-B6-C18; A19-B6-C19; A19-B6-C20;A19-B6-C21; A19-B6-C22; A19-B6-C23; A19-B6-C24; A19-B6-C25; A19-B6-C26;A19-B6-C27; A19-B6-C28; A19-B6-C29; A19-B6-C30; A19-B6-C31; A19-B6-C32;A19-B6-C33; A19-B6-C34; A19-B6-C35; A19-B6-C36; A19-B6-C37; A19-B6-C38;A19-B6-C39; A19-B6-C40; A19-B6-C41; A19-B6-C42; A19-B6-C43; A19-B6-C44;A19-B6-C45; A19-B6-C46; A20-B6-C1; A20-B6-C2; A20-B6-C3; A20-B6-C4;A20-B6-C5; A20-B6-C6; A20-B6-C7; A20-B6-C8; A20-B6-C9; A20-B6-C10;A20-B6-C11; A20-B6-C12; A20-B6-C13; A20-B6-C14; A20-B6-C15; A20-B6-C16;A20-B6-C17; A20-B6-C18; A20-B6-C19; A20-B6-C20; A20-B6-C21; A20-B6-C22;A20-B6-C23; A20-B6-C24; A20-B6-C25; A20-B6-C26; A20-B6-C27; A20-B6-C28;A20-B6-C29; A20-B6-C30; A20-B6-C31; A20-B6-C32; A20-B6-C33; A20-B6-C34;A20-B6-C35; A20-B6-C36; A20-B6-C37; A20-B6-C38; A20-B6-C39; A20-B6-C40;A20-B6-C41; A20-B6-C42; A20-B6-C43; A20-B6-C44; A20-B6-C45; A20-B6-C46;A21-B6-C1; A21-B6-C2; A21-B6-C3; A21-B6-C4; A21-B6-C5; A21-B6-C6;A21-B6-C7; A21-B6-C8; A21-B6-C9; A21-B6-C10; A21-B6-C11; A21-B6-C12;A21-B6-C13; A21-B6-C14; A21-B6-C15; A21-B6-C16; A21-B6-C17; A21-B6-C18;A21-B6-C19; A21-B6-C20; A21-B6-C21; A21-B6-C22; A21-B6-C23; A21-B6-C24;A21-B6-C25; A21-B6-C26; A21-B6-C27; A21-B6-C28; A21-B6-C29; A21-B6-C30;A21-B6-C31; A21-B6-C32; A21-B6-C33; A21-B6-C34; A21-B6-C35; A21-B6-C36;A21-B6-C37; A21-B6-C38; A21-B6-C39; A21-B6-C40; A21-B6-C41; A21-B6-C42;A21-B6-C43; A21-B6-C44; A21-B6-C45; A21-B6-C46; A22-B6-C1; A22-B6-C2;A22-B6-C3; A22-B6-C4; A22-B6-C5; A22-B6-C6; A22-B6-C7; A22-B6-C8;A22-B6-C9; A22-B6-C10; A22-B6-C11; A22-B6-C12; A22-B6-C13; A22-B6-C14;A22-B6-C15; A22-B6-C16; A22-B6-C17; A22-B6-C18; A22-B6-C19; A22-B6-C20;A22-B6-C21; A22-B6-C22; A22-B6-C23; A22-B6-C24; A22-B6-C25; A22-B6-C26;A22-B6-C27; A22-B6-C28; A22-B6-C29; A22-B6-C30; A22-B6-C31; A22-B6-C32;A22-B6-C33; A22-B6-C34; A22-B6-C35; A22-B6-C36; A22-B6-C37; A22-B6-C38;A22-B6-C39; A22-B6-C40; A22-B6-C41; A22-B6-C42; A22-B6-C43; A22-B6-C44;A22-B6-C45; A22-B6-C46; A23-B6-C1; A23-B6-C2; A23-B6-C3; A23-B6-C4;A23-B6-C5; A23-B6-C6; A23-B6-C7; A23-B6-C8; A23-B6-C9; A23-B6-C10;A23-B6-C11; A23-B6-C12; A23-B6-C13; A23-B6-C14; A23-B6-C15; A23-B6-C16;A23-B6-C17; A23-B6-C18; A23-B6-C19; A23-B6-C20; A23-B6-C21; A23-B6-C22;A23-B6-C23; A23-B6-C24; A23-B6-C25; A23-B6-C26; A23-B6-C27; A23-B6-C28;A23-B6-C29; A23-B6-C30; A23-B6-C31; A23-B6-C32; A23-B6-C33; A23-B6-C34;A23-B6-C35; A23-B6-C36; A23-B6-C37; A23-B6-C38; A23-B6-C39; A23-B6-C40;A23-B6-C41; A23-B6-C42; A23-B6-C43; A23-B6-C44; A23-B6-C45; A23-B6-C46;A24-B6-C1; A24-B6-C2; A24-B6-C3; A24-B6-C4; A24-B6-C5; A24-B6-C6;A24-B6-C7; A24-B6-C8; A24-B6-C9; A24-B6-C10; A24-B6-C11; A24-B6-C12;A24-B6-C13; A24-B6-C14; A24-B6-C15; A24-B6-C16; A24-B6-C17; A24-B6-C18;A24-B6-C19; A24-B6-C20; A24-B6-C21; A24-B6-C22; A24-B6-C23; A24-B6-C24;A24-B6-C25; A24-B6-C26; A24-B6-C27; A24-B6-C28; A24-B6-C29; A24-B6-C30;A24-B6-C31; A24-B6-C32; A24-B6-C33; A24-B6-C34; A24-B6-C35; A24-B6-C36;A24-B6-C37; A24-B6-C38; A24-B6-C39; A24-B6-C40; A24-B6-C41; A24-B6-C42;A24-B6-C43; A24-B6-C44; A24-B6-C45; A24-B6-C46; A25-B6-C1; A25-B6-C2;A25-B6-C3; A25-B6-C4; A25-B6-C5; A25-B6-C6; A25-B6-C7; A25-B6-C8;A25-B6-C9; A25-B6-C10; A25-B6-C11; A25-B6-C12; A25-B6-C13; A25-B6-C14;A25-B6-C15; A25-B6-C16; A25-B6-C17; A25-B6-C18; A25-B6-C19; A25-B6-C20;A25-B6-C21; A25-B6-C22; A25-B6-C23; A25-B6-C24; A25-B6-C25; A25-B6-C26;A25-B6-C27; A25-B6-C28; A25-B6-C29; A25-B6-C30; A25-B6-C31; A25-B6-C32;A25-B6-C33; A25-B6-C34; A25-B6-C35; A25-B6-C36; A25-B6-C37; A25-B6-C38;A25-B6-C39; A25-B6-C40; A25-B6-C41; A25-B6-C42; A25-B6-C43; A25-B6-C44;A25-B6-C45; A25-B6-C46; A26-B6-C1; A26-B6-C2; A26-B6-C3; A26-B6-C4;A26-B6-C5; A26-B6-C6; A26-B6-C7; A26-B6-C8; A26-B6-C9; A26-B6-C10;A26-B6-C11; A26-B6-C12; A26-B6-C13; A26-B6-C14; A26-B6-C15; A26-B6-C16;A26-B6-C17; A26-B6-C18; A26-B6-C19; A26-B6-C20; A26-B6-C21; A26-B6-C22;A26-B6-C23; A26-B6-C24; A26-B6-C25; A26-B6-C26; A26-B6-C27; A26-B6-C28;A26-B6-C29; A26-B6-C30; A26-B6-C31; A26-B6-C32; A26-B6-C33; A26-B6-C34;A26-B6-C35; A26-B6-C36; A26-B6-C37; A26-B6-C38; A26-B6-C39; A26-B6-C40;A26-B6-C41; A26-B6-C42; A26-B6-C43; A26-B6-C44; A26-B6-C45; A26-B6-C46;A27-B6-C1; A27-B6-C2; A27-B6-C3; A27-B6-C4; A27-B6-C5; A27-B6-C6;A27-B6-C7; A27-B6-C8; A27-B6-C9; A27-B6-C10; A27-B6-C11; A27-B6-C12;A27-B6-C13; A27-B6-C14; A27-B6-C15; A27-B6-C16; A27-B6-C17; A27-B6-C18;A27-B6-C19; A27-B6-C20; A27-B6-C21; A27-B6-C22; A27-B6-C23; A27-B6-C24;A27-B6-C25; A27-B6-C26; A27-B6-C27; A27-B6-C28; A27-B6-C29; A27-B6-C30;A27-B6-C31; A27-B6-C32; A27-B6-C33; A27-B6-C34; A27-B6-C35; A27-B6-C36;A27-B6-C37; A27-B6-C38; A27-B6-C39; A27-B6-C40; A27-B6-C41; A27-B6-C42;A27-B6-C43; A27-B6-C44; A27-B6-C45; A27-B6-C46; A28-B6-C1; A28-B6-C2;A28-B6-C3; A28-B6-C4; A28-B6-C5; A28-B6-C6; A28-B6-C7; A28-B6-C8;A28-B6-C9; A28-B6-C10; A28-B6-C11; A28-B6-C12; A28-B6-C13; A28-B6-C14;A28-B6-C15; A28-B6-C16; A28-B6-C17; A28-B6-C18; A28-B6-C19; A28-B6-C20;A28-B6-C21; A28-B6-C22; A28-B6-C23; A28-B6-C24; A28-B6-C25; A28-B6-C26;A28-B6-C27; A28-B6-C28; A28-B6-C29; A28-B6-C30; A28-B6-C31; A28-B6-C32;A28-B6-C33; A28-B6-C34; A28-B6-C35; A28-B6-C36; A28-B6-C37; A28-B6-C38;A28-B6-C39; A28-B6-C40; A28-B6-C41; A28-B6-C42; A28-B6-C43; A28-B6-C44;A28-B6-C45; A28-B6-C46; A1-B7-C1; A1-B7-C2; A1-B7-C3; A1-B7-C4;A1-B7-C5; A1-B7-C6; A1-B7-C7; A1-B7-C8; A1-B7-C9; A1-B7-C10; A1-B7-C11;A1-B7-C12; A1-B7-C13; A1-B7-C14; A1-B7-C15; A1-B7-C16; A1-B7-C17;A1-B7-C18; A1-B7-C19; A1-B7-C20; A1-B7-C21; A1-B7-C22; A1-B7-C23;A1-B7-C24; A1-B7-C25; A1-B7-C26; A1-B7-C27; A1-B7-C28; A1-B7-C29;A1-B7-C30; A1-B7-C31; A1-B7-C32; A1-B7-C33; A1-B7-C34; A1-B7-C35;A1-B7-C36; A1-B7-C37; A1-B7-C38; A1-B7-C39; A1-B7-C40; A1-B7-C41;A1-B7-C42; A1-B7-C43; A1-B7-C44; A1-B7-C45; A1-B7-C46; A2-B7-C1;A2-B7-C2; A2-B7-C3; A2-B7-C4; A2-B7-C5; A2-B7-C6; A2-B7-C7; A2-B7-C8;A2-B7-C9; A2-B7-C10; A2-B7-C11; A2-B7-C12; A2-B7-C13; A2-B7-C14;A2-B7-C15; A2-B7-C16; A2-B7-C17; A2-B7-C18; A2-B7-C19; A2-B7-C20;A2-B7-C21; A2-B7-C22; A2-B7-C23; A2-B7-C24; A2-B7-C25; A2-B7-C26;A2-B7-C27; A2-B7-C28; A2-B7-C29; A2-B7-C30; A2-B7-C31; A2-B7-C32;A2-B7-C33; A2-B7-C34; A2-B7-C35; A2-B7-C36; A2-B7-C37; A2-B7-C38;A2-B7-C39; A2-B7-C40; A2-B7-C41; A2-B7-C42; A2-B7-C43; A2-B7-C44;A2-B7-C45; A2-B7-C46; A3-B7-C1; A3-B7-C2; A3-B7-C3; A3-B7-C4; A3-B7-C5;A3-B7-C6; A3-B7-C7; A3-B7-C8; A3-B7-C9; A3-B7-C10; A3-B7-C11; A3-B7-C12;A3-B7-C13; A3-B7-C14; A3-B7-C15; A3-B7-C16; A3-B7-C17; A3-B7-C18;A3-B7-C19; A3-B7-C20; A3-B7-C21; A3-B7-C22; A3-B7-C23; A3-B7-C24;A3-B7-C25; A3-B7-C26; A3-B7-C27; A3-B7-C28; A3-B7-C29; A3-B7-C30;A3-B7-C31; A3-B7-C32; A3-B7-C33; A3-B7-C34; A3-B7-C35; A3-B7-C36;A3-B7-C37; A3-B7-C38; A3-B7-C39; A3-B7-C40; A3-B7-C41; A3-B7-C42;A3-B7-C43; A3-B7-C44; A3-B7-C45; A3-B7-C46; A4-B7-C1; A4-B7-C2;A4-B7-C3; A4-B7-C4; A4-B7-C5; A4-B7-C6; A4-B7-C7; A4-B7-C8; A4-B7-C9;A4-B7-C10; A4-B7-C11; A4-B7-C12; A4-B7-C13; A4-B7-C14; A4-B7-C15;A4-B7-C16; A4-B7-C17; A4-B7-C18; A4-B7-C19; A4-B7-C20; A4-B7-C21;A4-B7-C22; A4-B7-C23; A4-B7-C24; A4-B7-C25; A4-B7-C26; A4-B7-C27;A4-B7-C28; A4-B7-C29; A4-B7-C30; A4-B7-C31; A4-B7-C32; A4-B7-C33;A4-B7-C34; A4-B7-C35; A4-B7-C36; A4-B7-C37; A4-B7-C38; A4-B7-C39;A4-B7-C40; A4-B7-C41; A4-B7-C42; A4-B7-C43; A4-B7-C44; A4-B7-C45;A4-B7-C46; A5-B7-C1; A5-B7-C2; A5-B7-C3; A5-B7-C4; A5-B7-C5; A5-B7-C6;A5-B7-C7; A5-B7-C8; A5-B7-C9; A5-B7-C10; A5-B7-C11; A5-B7-C12;A5-B7-C13; A5-B7-C14; A5-B7-C15; A5-B7-C16; A5-B7-C17; A5-B7-C18;A5-B7-C19; A5-B7-C20; A5-B7-C21; A5-B7-C22; A5-B7-C23; A5-B7-C24;A5-B7-C25; A5-B7-C26; A5-B7-C27; A5-B7-C28; A5-B7-C29; A5-B7-C30;A5-B7-C31; A5-B7-C32; A5-B7-C33; A5-B7-C34; A5-B7-C35; A5-B7-C36;A5-B7-C37; A5-B7-C38; A5-B7-C39; A5-B7-C40; A5-B7-C41; A5-B7-C42;A5-B7-C43; A5-B7-C44; A5-B7-C45; A5-B7-C46; A6-B7-C1; A6-B7-C2;A6-B7-C3; A6-B7-C4; A6-B7-C5; A6-B7-C6; A6-B7-C7; A6-B7-C8; A6-B7-C9;A6-B7-C10; A6-B7-C11; A6-B7-C12; A6-B7-C13; A6-B7-C14; A6-B7-C15;A6-B7-C16; A6-B7-C17; A6-B7-C18; A6-B7-C19; A6-B7-C20; A6-B7-C21;A6-B7-C22; A6-B7-C23; A6-B7-C24; A6-B7-C25; A6-B7-C26; A6-B7-C27;A6-B7-C28; A6-B7-C29; A6-B7-C30; A6-B7-C31; A6-B7-C32; A6-B7-C33;A6-B7-C34; A6-B7-C35; A6-B7-C36; A6-B7-C37; A6-B7-C38; A6-B7-C39;A6-B7-C40; A6-B7-C41; A6-B7-C42; A6-B7-C43; A6-B7-C44; A6-B7-C45;A6-B7-C46; A7-B7-C1; A7-B7-C2; A7-B7-C3; A7-B7-C4; A7-B7-C5; A7-B7-C6;A7-B7-C7; A7-B7-C8; A7-B7-C9; A7-B7-C10; A7-B7-C11; A7-B7-C12;A7-B7-C13; A7-B7-C14; A7-B7-C15; A7-B7-C16; A7-B7-C17; A7-B7-C18;A7-B7-C19; A7-B7-C20; A7-B7-C21; A7-B7-C22; A7-B7-C23; A7-B7-C24;A7-B7-C25; A7-B7-C26; A7-B7-C27; A7-B7-C28; A7-B7-C29; A7-B7-C30;A7-B7-C31; A7-B7-C32; A7-B7-C33; A7-B7-C34; A7-B7-C35; A7-B7-C36;A7-B7-C37; A7-B7-C38; A7-B7-C39; A7-B7-C40; A7-B7-C41; A7-B7-C42;A7-B7-C43; A7-B7-C44; A7-B7-C45; A7-B7-C46; A8-B7-C1; A8-B7-C2;A8-B7-C3; A8-B7-C4; A8-B7-C5; A8-B7-C6; A8-B7-C7; A8-B7-C8; A8-B7-C9;A8-B7-C10; A8-B7-C11; A8-B7-C12; A8-B7-C13; A8-B7-C14; A8-B7-C15;A8-B7-C16; A8-B7-C17; A8-B7-C18; A8-B7-C19; A8-B7-C20; A8-B7-C21;A8-B7-C22; A8-B7-C23; A8-B7-C24; A8-B7-C25; A8-B7-C26; A8-B7-C27;A8-B7-C28; A8-B7-C29; A8-B7-C30; A8-B7-C31; A8-B7-C32; A8-B7-C33;A8-B7-C34; A8-B7-C35; A8-B7-C36; A8-B7-C37; A8-B7-C38; A8-B7-C39;A8-B7-C40; A8-B7-C41; A8-B7-C42; A8-B7-C43; A8-B7-C44; A8-B7-C45;A8-B7-C46; A9-B7-C1; A9-B7-C2; A9-B7-C3; A9-B7-C4; A9-B7-C5; A9-B7-C6;A9-B7-C7; A9-B7-C8; A9-B7-C9; A9-B7-C10; A9-B7-C11; A9-B7-C12;A9-B7-C13; A9-B7-C14; A9-B7-C15; A9-B7-C16; A9-B7-C17; A9-B7-C18;A9-B7-C19; A9-B7-C20; A9-B7-C21; A9-B7-C22; A9-B7-C23; A9-B7-C24;A9-B7-C25; A9-B7-C26; A9-B7-C27; A9-B7-C28; A9-B7-C29; A9-B7-C30;A9-B7-C31; A9-B7-C32; A9-B7-C33; A9-B7-C34; A9-B7-C35; A9-B7-C36;A9-B7-C37; A9-B7-C38; A9-B7-C39; A9-B7-C40; A9-B7-C41; A9-B7-C42;A9-B7-C43; A9-B7-C44; A9-B7-C45; A9-B7-C46; A10-B7-C1; A10-B7-C2;A10-B7-C3; A10-B7-C4; A10-B7-C5; A10-B7-C6; A10-B7-C7; A10-B7-C8;A10-B7-C9; A10-B7-C10; A10-B7-C11; A10-B7-C12; A10-B7-C13; A10-B7-C14;A10-B7-C15; A10-B7-C16; A10-B7-C17; A10-B7-C18; A10-B7-C19; A10-B7-C20;A10-B7-C21; A10-B7-C22; A10-B7-C23; A10-B7-C24; A10-B7-C25; A10-B7-C26;A10-B7-C27; A10-B7-C28; A10-B7-C29; A10-B7-C30; A10-B7-C31; A10-B7-C32;A10-B7-C33; A10-B7-C34; A10-B7-C35; A10-B7-C36; A10-B7-C37; A10-B7-C38;A10-B7-C39; A10-B7-C40; A10-B7-C41; A10-B7-C42; A10-B7-C43; A10-B7-C44;A10-B7-C45; A10-B7-C46; A11-B7-C1; A11-B7-C2; A11-B7-C3; A11-B7-C4;A11-B7-C5; A11-B7-C6; A11-B7-C7; A11-B7-C8; A11-B7-C9; A11-B7-C10;A11-B7-C11; A11-B7-C12; A11-B7-C13; A11-B7-C14; A11-B7-C15; A11-B7-C16;A11-B7-C17; A11-B7-C18; A11-B7-C19; A11-B7-C20; A11-B7-C21; A11-B7-C22;A11-B7-C23; A11-B7-C24; A11-B7-C25; A11-B7-C26; A11-B7-C27; A11-B7-C28;A11-B7-C29; A11-B7-C30; A11-B7-C31; A11-B7-C32; A11-B7-C33; A11-B7-C34;A11-B7-C35; A11-B7-C36; A11-B7-C37; A11-B7-C38; A11-B7-C39; A11-B7-C40;A11-B7-C41; A11-B7-C42; A11-B7-C43; A11-B7-C44; A11-B7-C45; A11-B7-C46;A12-B7-C1; A12-B7-C2; A12-B7-C3; A12-B7-C4; A12-B7-C5; A12-B7-C6;A12-B7-C7; A12-B7-C8; A12-B7-C9; A12-B7-C10; A12-B7-C11; A12-B7-C12;A12-B7-C13; A12-B7-C14; A12-B7-C15; A12-B7-C16; A12-B7-C17; A12-B7-C18;A12-B7-C19; A12-B7-C20; A12-B7-C21; A12-B7-C22; A12-B7-C23; A12-B7-C24;A12-B7-C25; A12-B7-C26; A12-B7-C27; A12-B7-C28; A12-B7-C29; A12-B7-C30;A12-B7-C31; A12-B7-C32; A12-B7-C33; A12-B7-C34; A12-B7-C35; A12-B7-C36;A12-B7-C37; A12-B7-C38; A12-B7-C39; A12-B7-C40; A12-B7-C41; A12-B7-C42;A12-B7-C43; A12-B7-C44; A12-B7-C45; A12-B7-C46; A13-B7-C1; A13-B7-C2;A13-B7-C3; A13-B7-C4; A13-B7-C5; A13-B7-C6; A13-B7-C7; A13-B7-C8;A13-B7-C9; A13-B7-C10; A13-B7-C11; A13-B7-C12; A13-B7-C13; A13-B7-C14;A13-B7-C15; A13-B7-C16; A13-B7-C17; A13-B7-C18; A13-B7-C19; A13-B7-C20;A13-B7-C21; A13-B7-C22; A13-B7-C23; A13-B7-C24; A13-B7-C25; A13-B7-C26;A13-B7-C27; A13-B7-C28; A13-B7-C29; A13-B7-C30; A13-B7-C31; A13-B7-C32;A13-B7-C33; A13-B7-C34; A13-B7-C35; A13-B7-C36; A13-B7-C37; A13-B7-C38;A13-B7-C39; A13-B7-C40; A13-B7-C41; A13-B7-C42; A13-B7-C43; A13-B7-C44;A13-B7-C45; A13-B7-C46; A14-B7-C1; A14-B7-C2; A14-B7-C3; A14-B7-C4;A14-B7-C5; A14-B7-C6; A14-B7-C7; A14-B7-C8; A14-B7-C9; A14-B7-C10;A14-B7-C11; A14-B7-C12; A14-B7-C13; A14-B7-C14; A14-B7-C15; A14-B7-C16;A14-B7-C17; A14-B7-C18; A14-B7-C19; A14-B7-C20; A14-B7-C21; A14-B7-C22;A14-B7-C23; A14-B7-C24; A14-B7-C25; A14-B7-C26; A14-B7-C27; A14-B7-C28;A14-B7-C29; A14-B7-C30; A14-B7-C31; A14-B7-C32; A14-B7-C33; A14-B7-C34;A14-B7-C35; A14-B7-C36; A14-B7-C37; A14-B7-C38; A14-B7-C39; A14-B7-C40;A14-B7-C41; A14-B7-C42; A14-B7-C43; A14-B7-C44; A14-B7-C45; A14-B7-C46;A15-B7-C1; A15-B7-C2; A15-B7-C3; A15-B7-C4; A15-B7-C5; A15-B7-C6;A15-B7-C7; A15-B7-C8; A15-B7-C9; A15-B7-C10; A15-B7-C11; A15-B7-C12;A15-B7-C13; A15-B7-C14; A15-B7-C15; A15-B7-C16; A15-B7-C17; A15-B7-C18;A15-B7-C19; A15-B7-C20; A15-B7-C21; A15-B7-C22; A15-B7-C23; A15-B7-C24;A15-B7-C25; A15-B7-C26; A15-B7-C27; A15-B7-C28; A15-B7-C29; A15-B7-C30;A15-B7-C31; A15-B7-C32; A15-B7-C33; A15-B7-C34; A15-B7-C35; A15-B7-C36;A15-B7-C37; A15-B7-C38; A15-B7-C39; A15-B7-C40; A15-B7-C41; A15-B7-C42;A15-B7-C43; A15-B7-C44; A15-B7-C45; A15-B7-C46; A16-B7-C1; A16-B7-C2;A16-B7-C3; A16-B7-C4; A16-B7-C5; A16-B7-C6; A16-B7-C7; A16-B7-C8;A16-B7-C9; A16-B7-C10; A16-B7-C11; A16-B7-C12; A16-B7-C13; A16-B7-C14;A16-B7-C15; A16-B7-C16; A16-B7-C17; A16-B7-C18; A16-B7-C19; A16-B7-C20;A16-B7-C21; A16-B7-C22; A16-B7-C23; A16-B7-C24; A16-B7-C25; A16-B7-C26;A16-B7-C27; A16-B7-C28; A16-B7-C29; A16-B7-C30; A16-B7-C31; A16-B7-C32;A16-B7-C33; A16-B7-C34; A16-B7-C35; A16-B7-C36; A16-B7-C37; A16-B7-C38;A16-B7-C39; A16-B7-C40; A16-B7-C41; A16-B7-C42; A16-B7-C43; A16-B7-C44;A16-B7-C45; A16-B7-C46; A17-B7-C1; A17-B7-C2; A17-B7-C3; A17-B7-C4;A17-B7-C5; A17-B7-C6; A17-B7-C7; A17-B7-C8; A17-B7-C9; A17-B7-C10;A17-B7-C11; A17-B7-C12; A17-B7-C13; A17-B7-C14; A17-B7-C15; A17-B7-C16;A17-B7-C17; A17-B7-C18; A17-B7-C19; A17-B7-C20; A17-B7-C21; A17-B7-C22;A17-B7-C23; A17-B7-C24; A17-B7-C25; A17-B7-C26; A17-B7-C27; A17-B7-C28;A17-B7-C29; A17-B7-C30; A17-B7-C31; A17-B7-C32; A17-B7-C33; A17-B7-C34;A17-B7-C35; A17-B7-C36; A17-B7-C37; A17-B7-C38; A17-B7-C39; A17-B7-C40;A17-B7-C41; A17-B7-C42; A17-B7-C43; A17-B7-C44; A17-B7-C45; A17-B7-C46;A18-B7-C1; A18-B7-C2; A18-B7-C3; A18-B7-C4; A18-B7-C5; A18-B7-C6;A18-B7-C7; A18-B7-C8; A18-B7-C9; A18-B7-C10; A18-B7-C11; A18-B7-C12;A18-B7-C13; A18-B7-C14; A18-B7-C15; A18-B7-C16; A18-B7-C17; A18-B7-C18;A18-B7-C19; A18-B7-C20; A18-B7-C21; A18-B7-C22; A18-B7-C23; A18-B7-C24;A18-B7-C25; A18-B7-C26; A18-B7-C27; A18-B7-C28; A18-B7-C29; A18-B7-C30;A18-B7-C31; A18-B7-C32; A18-B7-C33; A18-B7-C34; A18-B7-C35; A18-B7-C36;A18-B7-C37; A18-B7-C38; A18-B7-C39; A18-B7-C40; A18-B7-C41; A18-B7-C42;A18-B7-C43; A18-B7-C44; A18-B7-C45; A18-B7-C46; A19-B7-C1; A19-B7-C2;A19-B7-C3; A19-B7-C4; A19-B7-C5; A19-B7-C6; A19-B7-C7; A19-B7-C8;A19-B7-C9; A19-B7-C10; A19-B7-C11; A19-B7-C12; A19-B7-C13; A19-B7-C14;A19-B7-C15; A19-B7-C16; A19-B7-C17; A19-B7-C18; A19-B7-C19; A19-B7-C20;A19-B7-C21; A19-B7-C22; A19-B7-C23; A19-B7-C24; A19-B7-C25; A19-B7-C26;A19-B7-C27; A19-B7-C28; A19-B7-C29; A19-B7-C30; A19-B7-C31; A19-B7-C32;A19-B7-C33; A19-B7-C34; A19-B7-C35; A19-B7-C36; A19-B7-C37; A19-B7-C38;A19-B7-C39; A19-B7-C40; A19-B7-C41; A19-B7-C42; A19-B7-C43; A19-B7-C44;A19-B7-C45; A19-B7-C46; A20-B7-C1; A20-B7-C2; A20-B7-C3; A20-B7-C4;A20-B7-C5; A20-B7-C6; A20-B7-C7; A20-B7-C8; A20-B7-C9; A20-B7-C10;A20-B7-C11; A20-B7-C12; A20-B7-C13; A20-B7-C14; A20-B7-C15; A20-B7-C16;A20-B7-C17; A20-B7-C18; A20-B7-C19; A20-B7-C20; A20-B7-C21; A20-B7-C22;A20-B7-C23; A20-B7-C24; A20-B7-C25; A20-B7-C26; A20-B7-C27; A20-B7-C28;A20-B7-C29; A20-B7-C30; A20-B7-C31; A20-B7-C32; A20-B7-C33; A20-B7-C34;A20-B7-C35; A20-B7-C36; A20-B7-C37; A20-B7-C38; A20-B7-C39; A20-B7-C40;A20-B7-C41; A20-B7-C42; A20-B7-C43; A20-B7-C44; A20-B7-C45; A20-B7-C46;A21-B7-C1; A21-B7-C2; A21-B7-C3; A21-B7-C4; A21-B7-C5; A21-B7-C6;A21-B7-C7; A21-B7-C8; A21-B7-C9; A21-B7-C10; A21-B7-C11; A21-B7-C12;A21-B7-C13; A21-B7-C14; A21-B7-C15; A21-B7-C16; A21-B7-C17; A21-B7-C18;A21-B7-C19; A21-B7-C20; A21-B7-C21; A21-B7-C22; A21-B7-C23; A21-B7-C24;A21-B7-C25; A21-B7-C26; A21-B7-C27; A21-B7-C28; A21-B7-C29; A21-B7-C30;A21-B7-C31; A21-B7-C32; A21-B7-C33; A21-B7-C34; A21-B7-C35; A21-B7-C36;A21-B7-C37; A21-B7-C38; A21-B7-C39; A21-B7-C40; A21-B7-C41; A21-B7-C42;A21-B7-C43; A21-B7-C44; A21-B7-C45; A21-B7-C46; A22-B7-C1; A22-B7-C2;A22-B7-C3; A22-B7-C4; A22-B7-C5; A22-B7-C6; A22-B7-C7; A22-B7-C8;A22-B7-C9; A22-B7-C10; A22-B7-C11; A22-B7-C12; A22-B7-C13; A22-B7-C14;A22-B7-C15; A22-B7-C16; A22-B7-C17; A22-B7-C18; A22-B7-C19; A22-B7-C20;A22-B7-C21; A22-B7-C22; A22-B7-C23; A22-B7-C24; A22-B7-C25; A22-B7-C26;A22-B7-C27; A22-B7-C28; A22-B7-C29; A22-B7-C30; A22-B7-C31; A22-B7-C32;A22-B7-C33; A22-B7-C34; A22-B7-C35; A22-B7-C36; A22-B7-C37; A22-B7-C38;A22-B7-C39; A22-B7-C40; A22-B7-C41; A22-B7-C42; A22-B7-C43; A22-B7-C44;A22-B7-C45; A22-B7-C46; A23-B7-C1; A23-B7-C2; A23-B7-C3; A23-B7-C4;A23-B7-C5; A23-B7-C6; A23-B7-C7; A23-B7-C8; A23-B7-C9; A23-B7-C10;A23-B7-C11; A23-B7-C12; A23-B7-C13; A23-B7-C14; A23-B7-C15; A23-B7-C16;A23-B7-C17; A23-B7-C18; A23-B7-C19; A23-B7-C20; A23-B7-C21; A23-B7-C22;A23-B7-C23; A23-B7-C24; A23-B7-C25; A23-B7-C26; A23-B7-C27; A23-B7-C28;A23-B7-C29; A23-B7-C30; A23-B7-C31; A23-B7-C32; A23-B7-C33; A23-B7-C34;A23-B7-C35; A23-B7-C36; A23-B7-C37; A23-B7-C38; A23-B7-C39; A23-B7-C40;A23-B7-C41; A23-B7-C42; A23-B7-C43; A23-B7-C44; A23-B7-C45; A23-B7-C46;A24-B7-C1; A24-B7-C2; A24-B7-C3; A24-B7-C4; A24-B7-C5; A24-B7-C6;A24-B7-C7; A24-B7-C8; A24-B7-C9; A24-B7-C10; A24-B7-C11; A24-B7-C12;A24-B7-C13; A24-B7-C14; A24-B7-C15; A24-B7-C16; A24-B7-C17; A24-B7-C18;A24-B7-C19; A24-B7-C20; A24-B7-C21; A24-B7-C22; A24-B7-C23; A24-B7-C24;A24-B7-C25; A24-B7-C26; A24-B7-C27; A24-B7-C28; A24-B7-C29; A24-B7-C30;A24-B7-C31; A24-B7-C32; A24-B7-C33; A24-B7-C34; A24-B7-C35; A24-B7-C36;A24-B7-C37; A24-B7-C38; A24-B7-C39; A24-B7-C40; A24-B7-C41; A24-B7-C42;A24-B7-C43; A24-B7-C44; A24-B7-C45; A24-B7-C46; A25-B7-C1; A25-B7-C2;A25-B7-C3; A25-B7-C4; A25-B7-C5; A25-B7-C6; A25-B7-C7; A25-B7-C8;A25-B7-C9; A25-B7-C10; A25-B7-C11; A25-B7-C12; A25-B7-C13; A25-B7-C14;A25-B7-C15; A25-B7-C16; A25-B7-C17; A25-B7-C18; A25-B7-C19; A25-B7-C20;A25-B7-C21; A25-B7-C22; A25-B7-C23; A25-B7-C24; A25-B7-C25; A25-B7-C26;A25-B7-C27; A25-B7-C28; A25-B7-C29; A25-B7-C30; A25-B7-C31; A25-B7-C32;A25-B7-C33; A25-B7-C34; A25-B7-C35; A25-B7-C36; A25-B7-C37; A25-B7-C38;A25-B7-C39; A25-B7-C40; A25-B7-C41; A25-B7-C42; A25-B7-C43; A25-B7-C44;A25-B7-C45; A25-B7-C46; A26-B7-C1; A26-B7-C2; A26-B7-C3; A26-B7-C4;A26-B7-C5; A26-B7-C6; A26-B7-C7; A26-B7-C8; A26-B7-C9; A26-B7-C10;A26-B7-C11; A26-B7-C12; A26-B7-C13; A26-B7-C14; A26-B7-C15; A26-B7-C16;A26-B7-C17; A26-B7-C18; A26-B7-C19; A26-B7-C20; A26-B7-C21; A26-B7-C22;A26-B7-C23; A26-B7-C24; A26-B7-C25; A26-B7-C26; A26-B7-C27; A26-B7-C28;A26-B7-C29; A26-B7-C30; A26-B7-C31; A26-B7-C32; A26-B7-C33; A26-B7-C34;A26-B7-C35; A26-B7-C36; A26-B7-C37; A26-B7-C38; A26-B7-C39; A26-B7-C40;A26-B7-C41; A26-B7-C42; A26-B7-C43; A26-B7-C44; A26-B7-C45; A26-B7-C46;A27-B7-C1; A27-B7-C2; A27-B7-C3; A27-B7-C4; A27-B7-C5; A27-B7-C6;A27-B7-C7; A27-B7-C8; A27-B7-C9; A27-B7-C10; A27-B7-C11; A27-B7-C12;A27-B7-C13; A27-B7-C14; A27-B7-C15; A27-B7-C16; A27-B7-C17; A27-B7-C18;A27-B7-C19; A27-B7-C20; A27-B7-C21; A27-B7-C22; A27-B7-C23; A27-B7-C24;A27-B7-C25; A27-B7-C26; A27-B7-C27; A27-B7-C28; A27-B7-C29; A27-B7-C30;A27-B7-C31; A27-B7-C32; A27-B7-C33; A27-B7-C34; A27-B7-C35; A27-B7-C36;A27-B7-C37; A27-B7-C38; A27-B7-C39; A27-B7-C40; A27-B7-C41; A27-B7-C42;A27-B7-C43; A27-B7-C44; A27-B7-C45; A27-B7-C46; A28-B7-C1; A28-B7-C2;A28-B7-C3; A28-B7-C4; A28-B7-C5; A28-B7-C6; A28-B7-C7; A28-B7-C8;A28-B7-C9; A28-B7-C10; A28-B7-C11; A28-B7-C12; A28-B7-C13; A28-B7-C14;A28-B7-C15; A28-B7-C16; A28-B7-C17; A28-B7-C18; A28-B7-C19; A28-B7-C20;A28-B7-C21; A28-B7-C22; A28-B7-C23; A28-B7-C24; A28-B7-C25; A28-B7-C26;A28-B7-C27; A28-B7-C28; A28-B7-C29; A28-B7-C30; A28-B7-C31; A28-B7-C32;A28-B7-C33; A28-B7-C34; A28-B7-C35; A28-B7-C36; A28-B7-C37; A28-B7-C38;A28-B7-C39; A28-B7-C40; A28-B7-C41; A28-B7-C42; A28-B7-C43; A28-B7-C44;A28-B7-C45; A28-B7-C46; A1-B8-C1; A1-B8-C2; A1-B8-C3; A1-B8-C4;A1-B8-C5; A1-B8-C6; A1-B8-C7; A1-B8-C8; A1-B8-C9; A1-B8-C10; A1-B8-C11;A1-B8-C12; A1-B8-C13; A1-B8-C14; A1-B8-C15; A1-B8-C16; A1-B8-C17;A1-B8-C18; A1-B8-C19; A1-B8-C20; A1-B8-C21; A1-B8-C22; A1-B8-C23;A1-B8-C24; A1-B8-C25; A1-B8-C26; A1-B8-C27; A1-B8-C28; A1-B8-C29;A1-B8-C30; A1-B8-C31; A1-B8-C32; A1-B8-C33; A1-B8-C34; A1-B8-C35;A1-B8-C36; A1-B8-C37; A1-B8-C38; A1-B8-C39; A1-B8-C40; A1-B8-C41;A1-B8-C42; A1-B8-C43; A1-B8-C44; A1-B8-C45; A1-B8-C46; A2-B8-C1;A2-B8-C2; A2-B8-C3; A2-B8-C4; A2-B8-C5; A2-B8-C6; A2-B8-C7; A2-B8-C8;A2-B8-C9; A2-B8-C10; A2-B8-C11; A2-B8-C12; A2-B8-C13; A2-B8-C14;A2-B8-C15; A2-B8-C16; A2-B8-C17; A2-B8-C18; A2-B8-C19; A2-B8-C20;A2-B8-C21; A2-B8-C22; A2-B8-C23; A2-B8-C24; A2-B8-C25; A2-B8-C26;A2-B8-C27; A2-B8-C28; A2-B8-C29; A2-B8-C30; A2-B8-C31; A2-B8-C32;A2-B8-C33; A2-B8-C34; A2-B8-C35; A2-B8-C36; A2-B8-C37; A2-B8-C38;A2-B8-C39; A2-B8-C40; A2-B8-C41; A2-B8-C42; A2-B8-C43; A2-B8-C44;A2-B8-C45; A2-B8-C46; A3-B8-C1; A3-B8-C2; A3-B8-C3; A3-B8-C4; A3-B8-C5;A3-B8-C6; A3-B8-C7; A3-B8-C8; A3-B8-C9; A3-B8-C10; A3-B8-C11; A3-B8-C12;A3-B8-C13; A3-B8-C14; A3-B8-C15; A3-B8-C16; A3-B8-C17; A3-B8-C18;A3-B8-C19; A3-B8-C20; A3-B8-C21; A3-B8-C22; A3-B8-C23; A3-B8-C24;A3-B8-C25; A3-B8-C26; A3-B8-C27; A3-B8-C28; A3-B8-C29; A3-B8-C30;A3-B8-C31; A3-B8-C32; A3-B8-C33; A3-B8-C34; A3-B8-C35; A3-B8-C36;A3-B8-C37; A3-B8-C38; A3-B8-C39; A3-B8-C40; A3-B8-C41; A3-B8-C42;A3-B8-C43; A3-B8-C44; A3-B8-C45; A3-B8-C46; A4-B8-C1; A4-B8-C2;A4-B8-C3; A4-B8-C4; A4-B8-C5; A4-B8-C6; A4-B8-C7; A4-B8-C8; A4-B8-C9;A4-B8-C10; A4-B8-C11; A4-B8-C12; A4-B8-C13; A4-B8-C14; A4-B8-C15;A4-B8-C16; A4-B8-C17; A4-B8-C18; A4-B8-C19; A4-B8-C20; A4-B8-C21;A4-B8-C22; A4-B8-C23; A4-B8-C24; A4-B8-C25; A4-B8-C26; A4-B8-C27;A4-B8-C28; A4-B8-C29; A4-B8-C30; A4-B8-C31; A4-B8-C32; A4-B8-C33;A4-B8-C34; A4-B8-C35; A4-B8-C36; A4-B8-C37; A4-B8-C38; A4-B8-C39;A4-B8-C40; A4-B8-C41; A4-B8-C42; A4-B8-C43; A4-B8-C44; A4-B8-C45;A4-B8-C46; A5-B8-C1; A5-B8-C2; A5-B8-C3; A5-B8-C4; A5-B8-C5; A5-B8-C6;A5-B8-C7; A5-B8-C8; A5-B8-C9; A5-B8-C10; A5-B8-C11; A5-B8-C12;A5-B8-C13; A5-B8-C14; A5-B8-C15; A5-B8-C16; A5-B8-C17; A5-B8-C18;A5-B8-C19; A5-B8-C20; A5-B8-C21; A5-B8-C22; A5-B8-C23; A5-B8-C24;A5-B8-C25; A5-B8-C26; A5-B8-C27; A5-B8-C28; A5-B8-C29; A5-B8-C30;A5-B8-C31; A5-B8-C32; A5-B8-C33; A5-B8-C34; A5-B8-C35; A5-B8-C36;A5-B8-C37; A5-B8-C38; A5-B8-C39; A5-B8-C40; A5-B8-C41; A5-B8-C42;A5-B8-C43; A5-B8-C44; A5-B8-C45; A5-B8-C46; A6-B8-C1; A6-B8-C2;A6-B8-C3; A6-B8-C4; A6-B8-C5; A6-B8-C6; A6-B8-C7; A6-B8-C8; A6-B8-C9;A6-B8-C10; A6-B8-C11; A6-B8-C12; A6-B8-C13; A6-B8-C14; A6-B8-C15;A6-B8-C16; A6-B8-C17; A6-B8-C18; A6-B8-C19; A6-B8-C20; A6-B8-C21;A6-B8-C22; A6-B8-C23; A6-B8-C24; A6-B8-C25; A6-B8-C26; A6-B8-C27;A6-B8-C28; A6-B8-C29; A6-B8-C30; A6-B8-C31; A6-B8-C32; A6-B8-C33;A6-B8-C34; A6-B8-C35; A6-B8-C36; A6-B8-C37; A6-B8-C38; A6-B8-C39;A6-B8-C40; A6-B8-C41; A6-B8-C42; A6-B8-C43; A6-B8-C44; A6-B8-C45;A6-B8-C46; A7-B8-C1; A7-B8-C2; A7-B8-C3; A7-B8-C4; A7-B8-C5; A7-B8-C6;A7-B8-C7; A7-B8-C8; A7-B8-C9; A7-B8-C10; A7-B8-C11; A7-B8-C12;A7-B8-C13; A7-B8-C14; A7-B8-C15; A7-B8-C16; A7-B8-C17; A7-B8-C18;A7-B8-C19; A7-B8-C20; A7-B8-C21; A7-B8-C22; A7-B8-C23; A7-B8-C24;A7-B8-C25; A7-B8-C26; A7-B8-C27; A7-B8-C28; A7-B8-C29; A7-B8-C30;A7-B8-C31; A7-B8-C32; A7-B8-C33; A7-B8-C34; A7-B8-C35; A7-B8-C36;A7-B8-C37; A7-B8-C38; A7-B8-C39; A7-B8-C40; A7-B8-C41; A7-B8-C42;A7-B8-C43; A7-B8-C44; A7-B8-C45; A7-B8-C46; A8-B8-C1; A8-B8-C2;A8-B8-C3; A8-B8-C4; A8-B8-C5; A8-B8-C6; A8-B8-C7; A8-B8-C8; A8-B8-C9;A8-B8-C10; A8-B8-C11; A8-B8-C12; A8-B8-C13; A8-B8-C14; A8-B8-C15;A8-B8-C16; A8-B8-C17; A8-B8-C18; A8-B8-C19; A8-B8-C20; A8-B8-C21;A8-B8-C22; A8-B8-C23; A8-B8-C24; A8-B8-C25; A8-B8-C26; A8-B8-C27;A8-B8-C28; A8-B8-C29; A8-B8-C30; A8-B8-C31; A8-B8-C32; A8-B8-C33;A8-B8-C34; A8-B8-C35; A8-B8-C36; A8-B8-C37; A8-B8-C38; A8-B8-C39;A8-B8-C40; A8-B8-C41; A8-B8-C42; A8-B8-C43; A8-B8-C44; A8-B8-C45;A8-B8-C46; A9-B8-C1; A9-B8-C2; A9-B8-C3; A9-B8-C4; A9-B8-C5; A9-B8-C6;A9-B8-C7; A9-B8-C8; A9-B8-C9; A9-B8-C10; A9-B8-C11; A9-B8-C12;A9-B8-C13; A9-B8-C14; A9-B8-C15; A9-B8-C16; A9-B8-C17; A9-B8-C18;A9-B8-C19; A9-B8-C20; A9-B8-C21; A9-B8-C22; A9-B8-C23; A9-B8-C24;A9-B8-C25; A9-B8-C26; A9-B8-C27; A9-B8-C28; A9-B8-C29; A9-B8-C30;A9-B8-C31; A9-B8-C32; A9-B8-C33; A9-B8-C34; A9-B8-C35; A9-B8-C36;A9-B8-C37; A9-B8-C38; A9-B8-C39; A9-B8-C40; A9-B8-C41; A9-B8-C42;A9-B8-C43; A9-B8-C44; A9-B8-C45; A9-B8-C46; A10-B8-C1; A10-B8-C2;A10-B8-C3; A10-B8-C4; A10-B8-C5; A10-B8-C6; A10-B8-C7; A10-B8-C8;A10-B8-C9; A10-B8-C10; A10-B8-C11; A10-B8-C12; A10-B8-C13; A10-B8-C14;A10-B8-C15; A10-B8-C16; A10-B8-C17; A10-B8-C18; A10-B8-C19; A10-B8-C20;A10-B8-C21; A10-B8-C22; A10-B8-C23; A10-B8-C24; A10-B8-C25; A10-B8-C26;A10-B8-C27; A10-B8-C28; A10-B8-C29; A10-B8-C30; A10-B8-C31; A10-B8-C32;A10-B8-C33; A10-B8-C34; A10-B8-C35; A10-B8-C36; A10-B8-C37; A10-B8-C38;A10-B8-C39; A10-B8-C40; A10-B8-C41; A10-B8-C42; A10-B8-C43; A10-B8-C44;A10-B8-C45; A10-B8-C46; A11-B8-C1; A11-B8-C2; A11-B8-C3; A11-B8-C4;A11-B8-C5; A11-B8-C6; A11-B8-C7; A11-B8-C8; A11-B8-C9; A11-B8-C10;A11-B8-C11; A11-B8-C12; A11-B8-C13; A11-B8-C14; A11-B8-C15; A11-B8-C16;A11-B8-C17; A11-B8-C18; A11-B8-C19; A11-B8-C20; A11-B8-C21; A11-B8-C22;A11-B8-C23; A11-B8-C24; A11-B8-C25; A11-B8-C26; A11-B8-C27; A11-B8-C28;A11-B8-C29; A11-B8-C30; A11-B8-C31; A11-B8-C32; A11-B8-C33; A11-B8-C34;A11-B8-C35; A11-B8-C36; A11-B8-C37; A11-B8-C38; A11-B8-C39; A11-B8-C40;A11-B8-C41; A11-B8-C42; A11-B8-C43; A11-B8-C44; A11-B8-C45; A11-B8-C46;A12-B8-C1; A12-B8-C2; A12-B8-C3; A12-B8-C4; A12-B8-C5; A12-B8-C6;A12-B8-C7; A12-B8-C8; A12-B8-C9; A12-B8-C10; A12-B8-C11; A12-B8-C12;A12-B8-C13; A12-B8-C14; A12-B8-C15; A12-B8-C16; A12-B8-C17; A12-B8-C18;A12-B8-C19; A12-B8-C20; A12-B8-C21; A12-B8-C22; A12-B8-C23; A12-B8-C24;A12-B8-C25; A12-B8-C26; A12-B8-C27; A12-B8-C28; A12-B8-C29; A12-B8-C30;A12-B8-C31; A12-B8-C32; A12-B8-C33; A12-B8-C34; A12-B8-C35; A12-B8-C36;A12-B8-C37; A12-B8-C38; A12-B8-C39; A12-B8-C40; A12-B8-C41; A12-B8-C42;A12-B8-C43; A12-B8-C44; A12-B8-C45; A12-B8-C46; A13-B8-C1; A13-B8-C2;A13-B8-C3; A13-B8-C4; A13-B8-C5; A13-B8-C6; A13-B8-C7; A13-B8-C8;A13-B8-C9; A13-B8-C10; A13-B8-C11; A13-B8-C12; A13-B8-C13; A13-B8-C14;A13-B8-C15; A13-B8-C16; A13-B8-C17; A13-B8-C18; A13-B8-C19; A13-B8-C20;A13-B8-C21; A13-B8-C22; A13-B8-C23; A13-B8-C24; A13-B8-C25; A13-B8-C26;A13-B8-C27; A13-B8-C28; A13-B8-C29; A13-B8-C30; A13-B8-C31; A13-B8-C32;A13-B8-C33; A13-B8-C34; A13-B8-C35; A13-B8-C36; A13-B8-C37; A13-B8-C38;A13-B8-C39; A13-B8-C40; A13-B8-C41; A13-B8-C42; A13-B8-C43; A13-B8-C44;A13-B8-C45; A13-B8-C46; A14-B8-C1; A14-B8-C2; A14-B8-C3; A14-B8-C4;A14-B8-C5; A14-B8-C6; A14-B8-C7; A14-B8-C8; A14-B8-C9; A14-B8-C10;A14-B8-C11; A14-B8-C12; A14-B8-C13; A14-B8-C14; A14-B8-C15; A14-B8-C16;A14-B8-C17; A14-B8-C18; A14-B8-C19; A14-B8-C20; A14-B8-C21; A14-B8-C22;A14-B8-C23; A14-B8-C24; A14-B8-C25; A14-B8-C26; A14-B8-C27; A14-B8-C28;A14-B8-C29; A14-B8-C30; A14-B8-C31; A14-B8-C32; A14-B8-C33; A14-B8-C34;A14-B8-C35; A14-B8-C36; A14-B8-C37; A14-B8-C38; A14-B8-C39; A14-B8-C40;A14-B8-C41; A14-B8-C42; A14-B8-C43; A14-B8-C44; A14-B8-C45; A14-B8-C46;A15-B8-C1; A15-B8-C2; A15-B8-C3; A15-B8-C4; A15-B8-C5; A15-B8-C6;A15-B8-C7; A15-B8-C8; A15-B8-C9; A15-B8-C10; A15-B8-C11; A15-B8-C12;A15-B8-C13; A15-B8-C14; A15-B8-C15; A15-B8-C16; A15-B8-C17; A15-B8-C18;A15-B8-C19; A15-B8-C20; A15-B8-C21; A15-B8-C22; A15-B8-C23; A15-B8-C24;A15-B8-C25; A15-B8-C26; A15-B8-C27; A15-B8-C28; A15-B8-C29; A15-B8-C30;A15-B8-C31; A15-B8-C32; A15-B8-C33; A15-B8-C34; A15-B8-C35; A15-B8-C36;A15-B8-C37; A15-B8-C38; A15-B8-C39; A15-B8-C40; A15-B8-C41; A15-B8-C42;A15-B8-C43; A15-B8-C44; A15-B8-C45; A15-B8-C46; A16-B8-C1; A16-B8-C2;A16-B8-C3; A16-B8-C4; A16-B8-C5; A16-B8-C6; A16-B8-C7; A16-B8-C8;A16-B8-C9; A16-B8-C10; A16-B8-C11; A16-B8-C12; A16-B8-C13; A16-B8-C14;A16-B8-C15; A16-B8-C16; A16-B8-C17; A16-B8-C18; A16-B8-C19; A16-B8-C20;A16-B8-C21; A16-B8-C22; A16-B8-C23; A16-B8-C24; A16-B8-C25; A16-B8-C26;A16-B8-C27; A16-B8-C28; A16-B8-C29; A16-B8-C30; A16-B8-C31; A16-B8-C32;A16-B8-C33; A16-B8-C34; A16-B8-C35; A16-B8-C36; A16-B8-C37; A16-B8-C38;A16-B8-C39; A16-B8-C40; A16-B8-C41; A16-B8-C42; A16-B8-C43; A16-B8-C44;A16-B8-C45; A16-B8-C46; A17-B8-C1; A17-B8-C2; A17-B8-C3; A17-B8-C4;A17-B8-C5; A17-B8-C6; A17-B8-C7; A17-B8-C8; A17-B8-C9; A17-B8-C10;A17-B8-C11; A17-B8-C12; A17-B8-C13; A17-B8-C14; A17-B8-C15; A17-B8-C16;A17-B8-C17; A17-B8-C18; A17-B8-C19; A17-B8-C20; A17-B8-C21; A17-B8-C22;A17-B8-C23; A17-B8-C24; A17-B8-C25; A17-B8-C26; A17-B8-C27; A17-B8-C28;A17-B8-C29; A17-B8-C30; A17-B8-C31; A17-B8-C32; A17-B8-C33; A17-B8-C34;A17-B8-C35; A17-B8-C36; A17-B8-C37; A17-B8-C38; A17-B8-C39; A17-B8-C40;A17-B8-C41; A17-B8-C42; A17-B8-C43; A17-B8-C44; A17-B8-C45; A17-B8-C46;A18-B8-C1; A18-B8-C2; A18-B8-C3; A18-B8-C4; A18-B8-C5; A18-B8-C6;A18-B8-C7; A18-B8-C8; A18-B8-C9; A18-B8-C10; A18-B8-C11; A18-B8-C12;A18-B8-C13; A18-B8-C14; A18-B8-C15; A18-B8-C16; A18-B8-C17; A18-B8-C18;A18-B8-C19; A18-B8-C20; A18-B8-C21; A18-B8-C22; A18-B8-C23; A18-B8-C24;A18-B8-C25; A18-B8-C26; A18-B8-C27; A18-B8-C28; A18-B8-C29; A18-B8-C30;A18-B8-C31; A18-B8-C32; A18-B8-C33; A18-B8-C34; A18-B8-C35; A18-B8-C36;A18-B8-C37; A18-B8-C38; A18-B8-C39; A18-B8-C40; A18-B8-C41; A18-B8-C42;A18-B8-C43; A18-B8-C44; A18-B8-C45; A18-B8-C46; A19-B8-C1; A19-B8-C2;A19-B8-C3; A19-B8-C4; A19-B8-C5; A19-B8-C6; A19-B8-C7; A19-B8-C8;A19-B8-C9; A19-B8-C10; A19-B8-C11; A19-B8-C12; A19-B8-C13; A19-B8-C14;A19-B8-C15; A19-B8-C16; A19-B8-C17; A19-B8-C18; A19-B8-C19; A19-B8-C20;A19-B8-C21; A19-B8-C22; A19-B8-C23; A19-B8-C24; A19-B8-C25; A19-B8-C26;A19-B8-C27; A19-B8-C28; A19-B8-C29; A19-B8-C30; A19-B8-C31; A19-B8-C32;A19-B8-C33; A19-B8-C34; A19-B8-C35; A19-B8-C36; A19-B8-C37; A19-B8-C38;A19-B8-C39; A19-B8-C40; A19-B8-C41; A19-B8-C42; A19-B8-C43; A19-B8-C44;A19-B8-C45; A19-B8-C46; A20-B8-C1; A20-B8-C2; A20-B8-C3; A20-B8-C4;A20-B8-C5; A20-B8-C6; A20-B8-C7; A20-B8-C8; A20-B8-C9; A20-B8-C10;A20-B8-C11; A20-B8-C12; A20-B8-C13; A20-B8-C14; A20-B8-C15; A20-B8-C16;A20-B8-C17; A20-B8-C18; A20-B8-C19; A20-B8-C20; A20-B8-C21; A20-B8-C22;A20-B8-C23; A20-B8-C24; A20-B8-C25; A20-B8-C26; A20-B8-C27; A20-B8-C28;A20-B8-C29; A20-B8-C30; A20-B8-C31; A20-B8-C32; A20-B8-C33; A20-B8-C34;A20-B8-C35; A20-B8-C36; A20-B8-C37; A20-B8-C38; A20-B8-C39; A20-B8-C40;A20-B8-C41; A20-B8-C42; A20-B8-C43; A20-B8-C44; A20-B8-C45; A20-B8-C46;A21-B8-C1; A21-B8-C2; A21-B8-C3; A21-B8-C4; A21-B8-C5; A21-B8-C6;A21-B8-C7; A21-B8-C8; A21-B8-C9; A21-B8-C10; A21-B8-C11; A21-B8-C12;A21-B8-C13; A21-B8-C14; A21-B8-C15; A21-B8-C16; A21-B8-C17; A21-B8-C18;A21-B8-C19; A21-B8-C20; A21-B8-C21; A21-B8-C22; A21-B8-C23; A21-B8-C24;A21-B8-C25; A21-B8-C26; A21-B8-C27; A21-B8-C28; A21-B8-C29; A21-B8-C30;A21-B8-C31; A21-B8-C32; A21-B8-C33; A21-B8-C34; A21-B8-C35; A21-B8-C36;A21-B8-C37; A21-B8-C38; A21-B8-C39; A21-B8-C40; A21-B8-C41; A21-B8-C42;A21-B8-C43; A21-B8-C44; A21-B8-C45; A21-B8-C46; A22-B8-C1; A22-B8-C2;A22-B8-C3; A22-B8-C4; A22-B8-C5; A22-B8-C6; A22-B8-C7; A22-B8-C8;A22-B8-C9; A22-B8-C10; A22-B8-C11; A22-B8-C12; A22-B8-C13; A22-B8-C14;A22-B8-C15; A22-B8-C16; A22-B8-C17; A22-B8-C18; A22-B8-C19; A22-B8-C20;A22-B8-C21; A22-B8-C22; A22-B8-C23; A22-B8-C24; A22-B8-C25; A22-B8-C26;A22-B8-C27; A22-B8-C28; A22-B8-C29; A22-B8-C30; A22-B8-C31; A22-B8-C32;A22-B8-C33; A22-B8-C34; A22-B8-C35; A22-B8-C36; A22-B8-C37; A22-B8-C38;A22-B8-C39; A22-B8-C40; A22-B8-C41; A22-B8-C42; A22-B8-C43; A22-B8-C44;A22-B8-C45; A22-B8-C46; A23-B8-C1; A23-B8-C2; A23-B8-C3; A23-B8-C4;A23-B8-C5; A23-B8-C6; A23-B8-C7; A23-B8-C8; A23-B8-C9; A23-B8-C10;A23-B8-C11; A23-B8-C12; A23-B8-C13; A23-B8-C14; A23-B8-C15; A23-B8-C16;A23-B8-C17; A23-B8-C18; A23-B8-C19; A23-B8-C20; A23-B8-C21; A23-B8-C22;A23-B8-C23; A23-B8-C24; A23-B8-C25; A23-B8-C26; A23-B8-C27; A23-B8-C28;A23-B8-C29; A23-B8-C30; A23-B8-C31; A23-B8-C32; A23-B8-C33; A23-B8-C34;A23-B8-C35; A23-B8-C36; A23-B8-C37; A23-B8-C38; A23-B8-C39; A23-B8-C40;A23-B8-C41; A23-B8-C42; A23-B8-C43; A23-B8-C44; A23-B8-C45; A23-B8-C46;A24-B8-C1; A24-B8-C2; A24-B8-C3; A24-B8-C4; A24-B8-C5; A24-B8-C6;A24-B8-C7; A24-B8-C8; A24-B8-C9; A24-B8-C10; A24-B8-C11; A24-B8-C12;A24-B8-C13; A24-B8-C14; A24-B8-C15; A24-B8-C16; A24-B8-C17; A24-B8-C18;A24-B8-C19; A24-B8-C20; A24-B8-C21; A24-B8-C22; A24-B8-C23; A24-B8-C24;A24-B8-C25; A24-B8-C26; A24-B8-C27; A24-B8-C28; A24-B8-C29; A24-B8-C30;A24-B8-C31; A24-B8-C32; A24-B8-C33; A24-B8-C34; A24-B8-C35; A24-B8-C36;A24-B8-C37; A24-B8-C38; A24-B8-C39; A24-B8-C40; A24-B8-C41; A24-B8-C42;A24-B8-C43; A24-B8-C44; A24-B8-C45; A24-B8-C46; A25-B8-C1; A25-B8-C2;A25-B8-C3; A25-B8-C4; A25-B8-C5; A25-B8-C6; A25-B8-C7; A25-B8-C8;A25-B8-C9; A25-B8-C10; A25-B8-C11; A25-B8-C12; A25-B8-C13; A25-B8-C14;A25-B8-C15; A25-B8-C16; A25-B8-C17; A25-B8-C18; A25-B8-C19; A25-B8-C20;A25-B8-C21; A25-B8-C22; A25-B8-C23; A25-B8-C24; A25-B8-C25; A25-B8-C26;A25-B8-C27; A25-B8-C28; A25-B8-C29; A25-B8-C30; A25-B8-C31; A25-B8-C32;A25-B8-C33; A25-B8-C34; A25-B8-C35; A25-B8-C36; A25-B8-C37; A25-B8-C38;A25-B8-C39; A25-B8-C40; A25-B8-C41; A25-B8-C42; A25-B8-C43; A25-B8-C44;A25-B8-C45; A25-B8-C46; A26-B8-C1; A26-B8-C2; A26-B8-C3; A26-B8-C4;A26-B8-C5; A26-B8-C6; A26-B8-C7; A26-B8-C8; A26-B8-C9; A26-B8-C10;A26-B8-C11; A26-B8-C12; A26-B8-C13; A26-B8-C14; A26-B8-C15; A26-B8-C16;A26-B8-C17; A26-B8-C18; A26-B8-C19; A26-B8-C20; A26-B8-C21; A26-B8-C22;A26-B8-C23; A26-B8-C24; A26-B8-C25; A26-B8-C26; A26-B8-C27; A26-B8-C28;A26-B8-C29; A26-B8-C30; A26-B8-C31; A26-B8-C32; A26-B8-C33; A26-B8-C34;A26-B8-C35; A26-B8-C36; A26-B8-C37; A26-B8-C38; A26-B8-C39; A26-B8-C40;A26-B8-C41; A26-B8-C42; A26-B8-C43; A26-B8-C44; A26-B8-C45; A26-B8-C46;A27-B8-C1; A27-B8-C2; A27-B8-C3; A27-B8-C4; A27-B8-C5; A27-B8-C6;A27-B8-C7; A27-B8-C8; A27-B8-C9; A27-B8-C10; A27-B8-C11; A27-B8-C12;A27-B8-C13; A27-B8-C14; A27-B8-C15; A27-B8-C16; A27-B8-C17; A27-B8-C18;A27-B8-C19; A27-B8-C20; A27-B8-C21; A27-B8-C22; A27-B8-C23; A27-B8-C24;A27-B8-C25; A27-B8-C26; A27-B8-C27; A27-B8-C28; A27-B8-C29; A27-B8-C30;A27-B8-C31; A27-B8-C32; A27-B8-C33; A27-B8-C34; A27-B8-C35; A27-B8-C36;A27-B8-C37; A27-B8-C38; A27-B8-C39; A27-B8-C40; A27-B8-C41; A27-B8-C42;A27-B8-C43; A27-B8-C44; A27-B8-C45; A27-B8-C46; A28-B8-C1; A28-B8-C2;A28-B8-C3; A28-B8-C4; A28-B8-C5; A28-B8-C6; A28-B8-C7; A28-B8-C8;A28-B8-C9; A28-B8-C10; A28-B8-C11; A28-B8-C12; A28-B8-C13; A28-B8-C14;A28-B8-C15; A28-B8-C16; A28-B8-C17; A28-B8-C18; A28-B8-C19; A28-B8-C20;A28-B8-C21; A28-B8-C22; A28-B8-C23; A28-B8-C24; A28-B8-C25; A28-B8-C26;A28-B8-C27; A28-B8-C28; A28-B8-C29; A28-B8-C30; A28-B8-C31; A28-B8-C32;A28-B8-C33; A28-B8-C34; A28-B8-C35; A28-B8-C36; A28-B8-C37; A28-B8-C38;A28-B8-C39; A28-B8-C40; A28-B8-C41; A28-B8-C42; A28-B8-C43; A28-B8-C44;A28-B8-C45; A28-B8-C46; A1-B9-C1; A1-B9-C2; A1-B9-C3; A1-B9-C4;A1-B9-C5; A1-B9-C6; A1-B9-C7; A1-B9-C8; A1-B9-C9; A1-B9-C10; A1-B9-C11;A1-B9-C12; A1-B9-C13; A1-B9-C14; A1-B9-C15; A1-B9-C16; A1-B9-C17;A1-B9-C18; A1-B9-C19; A1-B9-C20; A1-B9-C21; A1-B9-C22; A1-B9-C23;A1-B9-C24; A1-B9-C25; A1-B9-C26; A1-B9-C27; A1-B9-C28; A1-B9-C29;A1-B9-C30; A1-B9-C31; A1-B9-C32; A1-B9-C33; A1-B9-C34; A1-B9-C35;A1-B9-C36; A1-B9-C37; A1-B9-C38; A1-B9-C39; A1-B9-C40; A1-B9-C41;A1-B9-C42; A1-B9-C43; A1-B9-C44; A1-B9-C45; A1-B9-C46; A2-B9-C1;A2-B9-C2; A2-B9-C3; A2-B9-C4; A2-B9-C5; A2-B9-C6; A2-B9-C7; A2-B9-C8;A2-B9-C9; A2-B9-C10; A2-B9-C11; A2-B9-C12; A2-B9-C13; A2-B9-C14;A2-B9-C15; A2-B9-C16; A2-B9-C17; A2-B9-C18; A2-B9-C19; A2-B9-C20;A2-B9-C21; A2-B9-C22; A2-B9-C23; A2-B9-C24; A2-B9-C25; A2-B9-C26;A2-B9-C27; A2-B9-C28; A2-B9-C29; A2-B9-C30; A2-B9-C31; A2-B9-C32;A2-B9-C33; A2-B9-C34; A2-B9-C35; A2-B9-C36; A2-B9-C37; A2-B9-C38;A2-B9-C39; A2-B9-C40; A2-B9-C41; A2-B9-C42; A2-B9-C43; A2-B9-C44;A2-B9-C45; A2-B9-C46; A3-B9-C1; A3-B9-C2; A3-B9-C3; A3-B9-C4; A3-B9-C5;A3-B9-C6; A3-B9-C7; A3-B9-C8; A3-B9-C9; A3-B9-C10; A3-B9-C11; A3-B9-C12;A3-B9-C13; A3-B9-C14; A3-B9-C15; A3-B9-C16; A3-B9-C17; A3-B9-C18;A3-B9-C19; A3-B9-C20; A3-B9-C21; A3-B9-C22; A3-B9-C23; A3-B9-C24;A3-B9-C25; A3-B9-C26; A3-B9-C27; A3-B9-C28; A3-B9-C29; A3-B9-C30;A3-B9-C31; A3-B9-C32; A3-B9-C33; A3-B9-C34; A3-B9-C35; A3-B9-C36;A3-B9-C37; A3-B9-C38; A3-B9-C39; A3-B9-C40; A3-B9-C41; A3-B9-C42;A3-B9-C43; A3-B9-C44; A3-B9-C45; A3-B9-C46; A4-B9-C1; A4-B9-C2;A4-B9-C3; A4-B9-C4; A4-B9-C5; A4-B9-C6; A4-B9-C7; A4-B9-C8; A4-B9-C9;A4-B9-C10; A4-B9-C11; A4-B9-C12; A4-B9-C13; A4-B9-C14; A4-B9-C15;A4-B9-C16; A4-B9-C17; A4-B9-C18; A4-B9-C19; A4-B9-C20; A4-B9-C21;A4-B9-C22; A4-B9-C23; A4-B9-C24; A4-B9-C25; A4-B9-C26; A4-B9-C27;A4-B9-C28; A4-B9-C29; A4-B9-C30; A4-B9-C31; A4-B9-C32; A4-B9-C33;A4-B9-C34; A4-B9-C35; A4-B9-C36; A4-B9-C37; A4-B9-C38; A4-B9-C39;A4-B9-C40; A4-B9-C41; A4-B9-C42; A4-B9-C43; A4-B9-C44; A4-B9-C45;A4-B9-C46; A5-B9-C1; A5-B9-C2; A5-B9-C3; A5-B9-C4; A5-B9-C5; A5-B9-C6;A5-B9-C7; A5-B9-C8; A5-B9-C9; A5-B9-C10; A5-B9-C11; A5-B9-C12;A5-B9-C13; A5-B9-C14; A5-B9-C15; A5-B9-C16; A5-B9-C17; A5-B9-C18;A5-B9-C19; A5-B9-C20; A5-B9-C21; A5-B9-C22; A5-B9-C23; A5-B9-C24;A5-B9-C25; A5-B9-C26; A5-B9-C27; A5-B9-C28; A5-B9-C29; A5-B9-C30;A5-B9-C31; A5-B9-C32; A5-B9-C33; A5-B9-C34; A5-B9-C35; A5-B9-C36;A5-B9-C37; A5-B9-C38; A5-B9-C39; A5-B9-C40; A5-B9-C41; A5-B9-C42;A5-B9-C43; A5-B9-C44; A5-B9-C45; A5-B9-C46; A6-B9-C1; A6-B9-C2;A6-B9-C3; A6-B9-C4; A6-B9-C5; A6-B9-C6; A6-B9-C7; A6-B9-C8; A6-B9-C9;A6-B9-C10; A6-B9-C11; A6-B9-C12; A6-B9-C13; A6-B9-C14; A6-B9-C15;A6-B9-C16; A6-B9-C17; A6-B9-C18; A6-B9-C19; A6-B9-C20; A6-B9-C21;A6-B9-C22; A6-B9-C23; A6-B9-C24; A6-B9-C25; A6-B9-C26; A6-B9-C27;A6-B9-C28; A6-B9-C29; A6-B9-C30; A6-B9-C31; A6-B9-C32; A6-B9-C33;A6-B9-C34; A6-B9-C35; A6-B9-C36; A6-B9-C37; A6-B9-C38; A6-B9-C39;A6-B9-C40; A6-B9-C41; A6-B9-C42; A6-B9-C43; A6-B9-C44; A6-B9-C45;A6-B9-C46; A7-B9-C1; A7-B9-C2; A7-B9-C3; A7-B9-C4; A7-B9-C5; A7-B9-C6;A7-B9-C7; A7-B9-C8; A7-B9-C9; A7-B9-C10; A7-B9-C11; A7-B9-C12;A7-B9-C13; A7-B9-C14; A7-B9-C15; A7-B9-C16; A7-B9-C17; A7-B9-C18;A7-B9-C19; A7-B9-C20; A7-B9-C21; A7-B9-C22; A7-B9-C23; A7-B9-C24;A7-B9-C25; A7-B9-C26; A7-B9-C27; A7-B9-C28; A7-B9-C29; A7-B9-C30;A7-B9-C31; A7-B9-C32; A7-B9-C33; A7-B9-C34; A7-B9-C35; A7-B9-C36;A7-B9-C37; A7-B9-C38; A7-B9-C39; A7-B9-C40; A7-B9-C41; A7-B9-C42;A7-B9-C43; A7-B9-C44; A7-B9-C45; A7-B9-C46; A8-B9-C1; A8-B9-C2;A8-B9-C3; A8-B9-C4; A8-B9-C5; A8-B9-C6; A8-B9-C7; A8-B9-C8; A8-B9-C9;A8-B9-C10; A8-B9-C11; A8-B9-C12; A8-B9-C13; A8-B9-C14; A8-B9-C15;A8-B9-C16; A8-B9-C17; A8-B9-C18; A8-B9-C19; A8-B9-C20; A8-B9-C21;A8-B9-C22; A8-B9-C23; A8-B9-C24; A8-B9-C25; A8-B9-C26; A8-B9-C27;A8-B9-C28; A8-B9-C29; A8-B9-C30; A8-B9-C31; A8-B9-C32; A8-B9-C33;A8-B9-C34; A8-B9-C35; A8-B9-C36; A8-B9-C37; A8-B9-C38; A8-B9-C39;A8-B9-C40; A8-B9-C41; A8-B9-C42; A8-B9-C43; A8-B9-C44; A8-B9-C45;A8-B9-C46; A9-B9-C1; A9-B9-C2; A9-B9-C3; A9-B9-C4; A9-B9-C5; A9-B9-C6;A9-B9-C7; A9-B9-C8; A9-B9-C9; A9-B9-C10; A9-B9-C11; A9-B9-C12;A9-B9-C13; A9-B9-C14; A9-B9-C15; A9-B9-C16; A9-B9-C17; A9-B9-C18;A9-B9-C19; A9-B9-C20; A9-B9-C21; A9-B9-C22; A9-B9-C23; A9-B9-C24;A9-B9-C25; A9-B9-C26; A9-B9-C27; A9-B9-C28; A9-B9-C29; A9-B9-C30;A9-B9-C31; A9-B9-C32; A9-B9-C33; A9-B9-C34; A9-B9-C35; A9-B9-C36;A9-B9-C37; A9-B9-C38; A9-B9-C39; A9-B9-C40; A9-B9-C41; A9-B9-C42;A9-B9-C43; A9-B9-C44; A9-B9-C45; A9-B9-C46; A10-B9-C1; A10-B9-C2;A10-B9-C3; A10-B9-C4; A10-B9-C5; A10-B9-C6; A10-B9-C7; A10-B9-C8;A10-B9-C9; A10-B9-C10; A10-B9-C11; A10-B9-C12; A10-B9-C13; A10-B9-C14;A10-B9-C15; A10-B9-C16; A10-B9-C17; A10-B9-C18; A10-B9-C19; A10-B9-C20;A10-B9-C21; A10-B9-C22; A10-B9-C23; A10-B9-C24; A10-B9-C25; A10-B9-C26;A10-B9-C27; A10-B9-C28; A10-B9-C29; A10-B9-C30; A10-B9-C31; A10-B9-C32;A10-B9-C33; A10-B9-C34; A10-B9-C35; A10-B9-C36; A10-B9-C37; A10-B9-C38;A10-B9-C39; A10-B9-C40; A10-B9-C41; A10-B9-C42; A10-B9-C43; A10-B9-C44;A10-B9-C45; A10-B9-C46; A11-B9-C1; A11-B9-C2; A11-B9-C3; A11-B9-C4;A11-B9-C5; A11-B9-C6; A11-B9-C7; A11-B9-C8; A11-B9-C9; A11-B9-C10;A11-B9-C11; A11-B9-C12; A11-B9-C13; A11-B9-C14; A11-B9-C15; A11-B9-C16;A11-B9-C17; A11-B9-C18; A11-B9-C19; A11-B9-C20; A11-B9-C21; A11-B9-C22;A11-B9-C23; A11-B9-C24; A11-B9-C25; A11-B9-C26; A11-B9-C27; A11-B9-C28;A11-B9-C29; A11-B9-C30; A11-B9-C31; A11-B9-C32; A11-B9-C33; A11-B9-C34;A11-B9-C35; A11-B9-C36; A11-B9-C37; A11-B9-C38; A11-B9-C39; A11-B9-C40;A11-B9-C41; A11-B9-C42; A11-B9-C43; A11-B9-C44; A11-B9-C45; A11-B9-C46;A12-B9-C1; A12-B9-C2; A12-B9-C3; A12-B9-C4; A12-B9-C5; A12-B9-C6;A12-B9-C7; A12-B9-C8; A12-B9-C9; A12-B9-C10; A12-B9-C11; A12-B9-C12;A12-B9-C13; A12-B9-C14; A12-B9-C15; A12-B9-C16; A12-B9-C17; A12-B9-C18;A12-B9-C19; A12-B9-C20; A12-B9-C21; A12-B9-C22; A12-B9-C23; A12-B9-C24;A12-B9-C25; A12-B9-C26; A12-B9-C27; A12-B9-C28; A12-B9-C29; A12-B9-C30;A12-B9-C31; A12-B9-C32; A12-B9-C33; A12-B9-C34; A12-B9-C35; A12-B9-C36;A12-B9-C37; A12-B9-C38; A12-B9-C39; A12-B9-C40; A12-B9-C41; A12-B9-C42;A12-B9-C43; A12-B9-C44; A12-B9-C45; A12-B9-C46; A13-B9-C1; A13-B9-C2;A13-B9-C3; A13-B9-C4; A13-B9-C5; A13-B9-C6; A13-B9-C7; A13-B9-C8;A13-B9-C9; A13-B9-C10; A13-B9-C11; A13-B9-C12; A13-B9-C13; A13-B9-C14;A13-B9-C15; A13-B9-C16; A13-B9-C17; A13-B9-C18; A13-B9-C19; A13-B9-C20;A13-B9-C21; A13-B9-C22; A13-B9-C23; A13-B9-C24; A13-B9-C25; A13-B9-C26;A13-B9-C27; A13-B9-C28; A13-B9-C29; A13-B9-C30; A13-B9-C31; A13-B9-C32;A13-B9-C33; A13-B9-C34; A13-B9-C35; A13-B9-C36; A13-B9-C37; A13-B9-C38;A13-B9-C39; A13-B9-C40; A13-B9-C41; A13-B9-C42; A13-B9-C43; A13-B9-C44;A13-B9-C45; A13-B9-C46; A14-B9-C1; A14-B9-C2; A14-B9-C3; A14-B9-C4;A14-B9-C5; A14-B9-C6; A14-B9-C7; A14-B9-C8; A14-B9-C9; A14-B9-C10;A14-B9-C11; A14-B9-C12; A14-B9-C13; A14-B9-C14; A14-B9-C15; A14-B9-C16;A14-B9-C17; A14-B9-C18; A14-B9-C19; A14-B9-C20; A14-B9-C21; A14-B9-C22;A14-B9-C23; A14-B9-C24; A14-B9-C25; A14-B9-C26; A14-B9-C27; A14-B9-C28;A14-B9-C29; A14-B9-C30; A14-B9-C31; A14-B9-C32; A14-B9-C33; A14-B9-C34;A14-B9-C35; A14-B9-C36; A14-B9-C37; A14-B9-C38; A14-B9-C39; A14-B9-C40;A14-B9-C41; A14-B9-C42; A14-B9-C43; A14-B9-C44; A14-B9-C45; A14-B9-C46;A15-B9-C1; A15-B9-C2; A15-B9-C3; A15-B9-C4; A15-B9-C5; A15-B9-C6;A15-B9-C7; A15-B9-C8; A15-B9-C9; A15-B9-C10; A15-B9-C11; A15-B9-C12;A15-B9-C13; A15-B9-C14; A15-B9-C15; A15-B9-C16; A15-B9-C17; A15-B9-C18;A15-B9-C19; A15-B9-C20; A15-B9-C21; A15-B9-C22; A15-B9-C23; A15-B9-C24;A15-B9-C25; A15-B9-C26; A15-B9-C27; A15-B9-C28; A15-B9-C29; A15-B9-C30;A15-B9-C31; A15-B9-C32; A15-B9-C33; A15-B9-C34; A15-B9-C35; A15-B9-C36;A15-B9-C37; A15-B9-C38; A15-B9-C39; A15-B9-C40; A15-B9-C41; A15-B9-C42;A15-B9-C43; A15-B9-C44; A15-B9-C45; A15-B9-C46; A16-B9-C1; A16-B9-C2;A16-B9-C3; A16-B9-C4; A16-B9-C5; A16-B9-C6; A16-B9-C7; A16-B9-C8;A16-B9-C9; A16-B9-C10; A16-B9-C11; A16-B9-C12; A16-B9-C13; A16-B9-C14;A16-B9-C15; A16-B9-C16; A16-B9-C17; A16-B9-C18; A16-B9-C19; A16-B9-C20;A16-B9-C21; A16-B9-C22; A16-B9-C23; A16-B9-C24; A16-B9-C25; A16-B9-C26;A16-B9-C27; A16-B9-C28; A16-B9-C29; A16-B9-C30; A16-B9-C31; A16-B9-C32;A16-B9-C33; A16-B9-C34; A16-B9-C35; A16-B9-C36; A16-B9-C37; A16-B9-C38;A16-B9-C39; A16-B9-C40; A16-B9-C41; A16-B9-C42; A16-B9-C43; A16-B9-C44;A16-B9-C45; A16-B9-C46; A17-B9-C1; A17-B9-C2; A17-B9-C3; A17-B9-C4;A17-B9-C5; A17-B9-C6; A17-B9-C7; A17-B9-C8; A17-B9-C9; A17-B9-C10;A17-B9-C11; A17-B9-C12; A17-B9-C13; A17-B9-C14; A17-B9-C15; A17-B9-C16;A17-B9-C17; A17-B9-C18; A17-B9-C19; A17-B9-C20; A17-B9-C21; A17-B9-C22;A17-B9-C23; A17-B9-C24; A17-B9-C25; A17-B9-C26; A17-B9-C27; A17-B9-C28;A17-B9-C29; A17-B9-C30; A17-B9-C31; A17-B9-C32; A17-B9-C33; A17-B9-C34;A17-B9-C35; A17-B9-C36; A17-B9-C37; A17-B9-C38; A17-B9-C39; A17-B9-C40;A17-B9-C41; A17-B9-C42; A17-B9-C43; A17-B9-C44; A17-B9-C45; A17-B9-C46;A18-B9-C1; A18-B9-C2; A18-B9-C3; A18-B9-C4; A18-B9-C5; A18-B9-C6;A18-B9-C7; A18-B9-C8; A18-B9-C9; A18-B9-C10; A18-B9-C11; A18-B9-C12;A18-B9-C13; A18-B9-C14; A18-B9-C15; A18-B9-C16; A18-B9-C17; A18-B9-C18;A18-B9-C19; A18-B9-C20; A18-B9-C21; A18-B9-C22; A18-B9-C23; A18-B9-C24;A18-B9-C25; A18-B9-C26; A18-B9-C27; A18-B9-C28; A18-B9-C29; A18-B9-C30;A18-B9-C31; A18-B9-C32; A18-B9-C33; A18-B9-C34; A18-B9-C35; A18-B9-C36;A18-B9-C37; A18-B9-C38; A18-B9-C39; A18-B9-C40; A18-B9-C41; A18-B9-C42;A18-B9-C43; A18-B9-C44; A18-B9-C45; A18-B9-C46; A19-B9-C1; A19-B9-C2;A19-B9-C3; A19-B9-C4; A19-B9-C5; A19-B9-C6; A19-B9-C7; A19-B9-C8;A19-B9-C9; A19-B9-C10; A19-B9-C11; A19-B9-C12; A19-B9-C13; A19-B9-C14;A19-B9-C15; A19-B9-C16; A19-B9-C17; A19-B9-C18; A19-B9-C19; A19-B9-C20;A19-B9-C21; A19-B9-C22; A19-B9-C23; A19-B9-C24; A19-B9-C25; A19-B9-C26;A19-B9-C27; A19-B9-C28; A19-B9-C29; A19-B9-C30; A19-B9-C31; A19-B9-C32;A19-B9-C33; A19-B9-C34; A19-B9-C35; A19-B9-C36; A19-B9-C37; A19-B9-C38;A19-B9-C39; A19-B9-C40; A19-B9-C41; A19-B9-C42; A19-B9-C43; A19-B9-C44;A19-B9-C45; A19-B9-C46; A20-B9-C1; A20-B9-C2; A20-B9-C3; A20-B9-C4;A20-B9-C5; A20-B9-C6; A20-B9-C7; A20-B9-C8; A20-B9-C9; A20-B9-C10;A20-B9-C11; A20-B9-C12; A20-B9-C13; A20-B9-C14; A20-B9-C15; A20-B9-C16;A20-B9-C17; A20-B9-C18; A20-B9-C19; A20-B9-C20; A20-B9-C21; A20-B9-C22;A20-B9-C23; A20-B9-C24; A20-B9-C25; A20-B9-C26; A20-B9-C27; A20-B9-C28;A20-B9-C29; A20-B9-C30; A20-B9-C31; A20-B9-C32; A20-B9-C33; A20-B9-C34;A20-B9-C35; A20-B9-C36; A20-B9-C37; A20-B9-C38; A20-B9-C39; A20-B9-C40;A20-B9-C41; A20-B9-C42; A20-B9-C43; A20-B9-C44; A20-B9-C45; A20-B9-C46;A21-B9-C1; A21-B9-C2; A21-B9-C3; A21-B9-C4; A21-B9-C5; A21-B9-C6;A21-B9-C7; A21-B9-C8; A21-B9-C9; A21-B9-C10; A21-B9-C11; A21-B9-C12;A21-B9-C13; A21-B9-C14; A21-B9-C15; A21-B9-C16; A21-B9-C17; A21-B9-C18;A21-B9-C19; A21-B9-C20; A21-B9-C21; A21-B9-C22; A21-B9-C23; A21-B9-C24;A21-B9-C25; A21-B9-C26; A21-B9-C27; A21-B9-C28; A21-B9-C29; A21-B9-C30;A21-B9-C31; A21-B9-C32; A21-B9-C33; A21-B9-C34; A21-B9-C35; A21-B9-C36;A21-B9-C37; A21-B9-C38; A21-B9-C39; A21-B9-C40; A21-B9-C41; A21-B9-C42;A21-B9-C43; A21-B9-C44; A21-B9-C45; A21-B9-C46; A22-B9-C1; A22-B9-C2;A22-B9-C3; A22-B9-C4; A22-B9-C5; A22-B9-C6; A22-B9-C7; A22-B9-C8;A22-B9-C9; A22-B9-C10; A22-B9-C11; A22-B9-C12; A22-B9-C13; A22-B9-C14;A22-B9-C15; A22-B9-C16; A22-B9-C17; A22-B9-C18; A22-B9-C19; A22-B9-C20;A22-B9-C21; A22-B9-C22; A22-B9-C23; A22-B9-C24; A22-B9-C25; A22-B9-C26;A22-B9-C27; A22-B9-C28; A22-B9-C29; A22-B9-C30; A22-B9-C31; A22-B9-C32;A22-B9-C33; A22-B9-C34; A22-B9-C35; A22-B9-C36; A22-B9-C37; A22-B9-C38;A22-B9-C39; A22-B9-C40; A22-B9-C41; A22-B9-C42; A22-B9-C43; A22-B9-C44;A22-B9-C45; A22-B9-C46; A23-B9-C1; A23-B9-C2; A23-B9-C3; A23-B9-C4;A23-B9-C5; A23-B9-C6; A23-B9-C7; A23-B9-C8; A23-B9-C9; A23-B9-C10;A23-B9-C11; A23-B9-C12; A23-B9-C13; A23-B9-C14; A23-B9-C15; A23-B9-C16;A23-B9-C17; A23-B9-C18; A23-B9-C19; A23-B9-C20; A23-B9-C21; A23-B9-C22;A23-B9-C23; A23-B9-C24; A23-B9-C25; A23-B9-C26; A23-B9-C27; A23-B9-C28;A23-B9-C29; A23-B9-C30; A23-B9-C31; A23-B9-C32; A23-B9-C33; A23-B9-C34;A23-B9-C35; A23-B9-C36; A23-B9-C37; A23-B9-C38; A23-B9-C39; A23-B9-C40;A23-B9-C41; A23-B9-C42; A23-B9-C43; A23-B9-C44; A23-B9-C45; A23-B9-C46;A24-B9-C1; A24-B9-C2; A24-B9-C3; A24-B9-C4; A24-B9-C5; A24-B9-C6;A24-B9-C7; A24-B9-C8; A24-B9-C9; A24-B9-C10; A24-B9-C11; A24-B9-C12;A24-B9-C13; A24-B9-C14; A24-B9-C15; A24-B9-C16; A24-B9-C17; A24-B9-C18;A24-B9-C19; A24-B9-C20; A24-B9-C21; A24-B9-C22; A24-B9-C23; A24-B9-C24;A24-B9-C25; A24-B9-C26; A24-B9-C27; A24-B9-C28; A24-B9-C29; A24-B9-C30;A24-B9-C31; A24-B9-C32; A24-B9-C33; A24-B9-C34; A24-B9-C35; A24-B9-C36;A24-B9-C37; A24-B9-C38; A24-B9-C39; A24-B9-C40; A24-B9-C41; A24-B9-C42;A24-B9-C43; A24-B9-C44; A24-B9-C45; A24-B9-C46; A25-B9-C1; A25-B9-C2;A25-B9-C3; A25-B9-C4; A25-B9-C5; A25-B9-C6; A25-B9-C7; A25-B9-C8;A25-B9-C9; A25-B9-C10; A25-B9-C11; A25-B9-C12; A25-B9-C13; A25-B9-C14;A25-B9-C15; A25-B9-C16; A25-B9-C17; A25-B9-C18; A25-B9-C19; A25-B9-C20;A25-B9-C21; A25-B9-C22; A25-B9-C23; A25-B9-C24; A25-B9-C25; A25-B9-C26;A25-B9-C27; A25-B9-C28; A25-B9-C29; A25-B9-C30; A25-B9-C31; A25-B9-C32;A25-B9-C33; A25-B9-C34; A25-B9-C35; A25-B9-C36; A25-B9-C37; A25-B9-C38;A25-B9-C39; A25-B9-C40; A25-B9-C41; A25-B9-C42; A25-B9-C43; A25-B9-C44;A25-B9-C45; A25-B9-C46; A26-B9-C1; A26-B9-C2; A26-B9-C3; A26-B9-C4;A26-B9-C5; A26-B9-C6; A26-B9-C7; A26-B9-C8; A26-B9-C9; A26-B9-C10;A26-B9-C11; A26-B9-C12; A26-B9-C13; A26-B9-C14; A26-B9-C15; A26-B9-C16;A26-B9-C17; A26-B9-C18; A26-B9-C19; A26-B9-C20; A26-B9-C21; A26-B9-C22;A26-B9-C23; A26-B9-C24; A26-B9-C25; A26-B9-C26; A26-B9-C27; A26-B9-C28;A26-B9-C29; A26-B9-C30; A26-B9-C31; A26-B9-C32; A26-B9-C33; A26-B9-C34;A26-B9-C35; A26-B9-C36; A26-B9-C37; A26-B9-C38; A26-B9-C39; A26-B9-C40;A26-B9-C41; A26-B9-C42; A26-B9-C43; A26-B9-C44; A26-B9-C45; A26-B9-C46;A27-B9-C1; A27-B9-C2; A27-B9-C3; A27-B9-C4; A27-B9-C5; A27-B9-C6;A27-B9-C7; A27-B9-C8; A27-B9-C9; A27-B9-C10; A27-B9-C11; A27-B9-C12;A27-B9-C13; A27-B9-C14; A27-B9-C15; A27-B9-C16; A27-B9-C17; A27-B9-C18;A27-B9-C19; A27-B9-C20; A27-B9-C21; A27-B9-C22; A27-B9-C23; A27-B9-C24;A27-B9-C25; A27-B9-C26; A27-B9-C27; A27-B9-C28; A27-B9-C29; A27-B9-C30;A27-B9-C31; A27-B9-C32; A27-B9-C33; A27-B9-C34; A27-B9-C35; A27-B9-C36;A27-B9-C37; A27-B9-C38; A27-B9-C39; A27-B9-C40; A27-B9-C41; A27-B9-C42;A27-B9-C43; A27-B9-C44; A27-B9-C45; A27-B9-C46; A28-B9-C1; A28-B9-C2;A28-B9-C3; A28-B9-C4; A28-B9-C5; A28-B9-C6; A28-B9-C7; A28-B9-C8;A28-B9-C9; A28-B9-C10; A28-B9-C11; A28-B9-C12; A28-B9-C13; A28-B9-C14;A28-B9-C15; A28-B9-C16; A28-B9-C17; A28-B9-C18; A28-B9-C19; A28-B9-C20;A28-B9-C21; A28-B9-C22; A28-B9-C23; A28-B9-C24; A28-B9-C25; A28-B9-C26;A28-B9-C27; A28-B9-C28; A28-B9-C29; A28-B9-C30; A28-B9-C31; A28-B9-C32;A28-B9-C33; A28-B9-C34; A28-B9-C35; A28-B9-C36; A28-B9-C37; A28-B9-C38;A28-B9-C39; A28-B9-C40; A28-B9-C41; A28-B9-C42; A28-B9-C43; A28-B9-C44;A28-B9-C45; A28-B9-C46; A1-B10-C1; A1-B10-C2; A1-B10-C3; A1-B10-C4;A1-B10-C5; A1-B10-C6; A1-B10-C7; A1-B10-C8; A1-B10-C9; A1-B10-C10;A1-B10-C11; A1-B10-C12; A1-B10-C13; A1-B10-C14; A1-B10-C15; A1-B10-C16;A1-B10-C17; A1-B10-C18; A1-B10-C19; A1-B10-C20; A1-B10-C21; A1-B10-C22;A1-B10-C23; A1-B10-C24; A1-B10-C25; A1-B10-C26; A1-B10-C27; A1-B10-C28;A1-B10-C29; A1-B10-C30; A1-B10-C31; A1-B10-C32; A1-B10-C33; A1-B10-C34;A1-B10-C35; A1-B10-C36; A1-B10-C37; A1-B10-C38; A1-B10-C39; A1-B10-C40;A1-B10-C41; A1-B10-C42; A1-B10-C43; A1-B10-C44; A1-B10-C45; A1-B10-C46;A2-B10-C1; A2-B10-C2; A2-B10-C3; A2-B10-C4; A2-B10-C5; A2-B10-C6;A2-B10-C7; A2-B10-C8; A2-B10-C9; A2-B10-C10; A2-B10-C11; A2-B10-C12;A2-B10-C13; A2-B10-C14; A2-B10-C15; A2-B10-C16; A2-B10-C17; A2-B10-C18;A2-B10-C19; A2-B10-C20; A2-B10-C21; A2-B10-C22; A2-B10-C23; A2-B10-C24;A2-B10-C25; A2-B10-C26; A2-B10-C27; A2-B10-C28; A2-B10-C29; A2-B10-C30;A2-B10-C31; A2-B10-C32; A2-B10-C33; A2-B10-C34; A2-B10-C35; A2-B10-C36;A2-B10-C37; A2-B10-C38; A2-B10-C39; A2-B10-C40; A2-B10-C41; A2-B10-C42;A2-B10-C43; A2-B10-C44; A2-B10-C45; A2-B10-C46; A3-B10-C1; A3-B10-C2;A3-B10-C3; A3-B10-C4; A3-B10-C5; A3-B10-C6; A3-B10-C7; A3-B10-C8;A3-B10-C9; A3-B10-C10; A3-B10-C11; A3-B10-C12; A3-B10-C13; A3-B10-C14;A3-B10-C15; A3-B10-C16; A3-B10-C17; A3-B10-C18; A3-B10-C19; A3-B10-C20;A3-B10-C21; A3-B10-C22; A3-B10-C23; A3-B10-C24; A3-B10-C25; A3-B10-C26;A3-B10-C27; A3-B10-C28; A3-B10-C29; A3-B10-C30; A3-B10-C31; A3-B10-C32;A3-B10-C33; A3-B10-C34; A3-B10-C35; A3-B10-C36; A3-B10-C37; A3-B10-C38;A3-B10-C39; A3-B10-C40; A3-B10-C41; A3-B10-C42; A3-B10-C43; A3-B10-C44;A3-B10-C45; A3-B10-C46; A4-B10-C1; A4-B10-C2; A4-B10-C3; A4-B10-C4;A4-B10-C5; A4-B10-C6; A4-B10-C7; A4-B10-C8; A4-B10-C9; A4-B10-C10;A4-B10-C11; A4-B10-C12; A4-B10-C13; A4-B10-C14; A4-B10-C15; A4-B10-C16;A4-B10-C17; A4-B10-C18; A4-B10-C19; A4-B10-C20; A4-B10-C21; A4-B10-C22;A4-B10-C23; A4-B10-C24; A4-B10-C25; A4-B10-C26; A4-B10-C27; A4-B10-C28;A4-B10-C29; A4-B10-C30; A4-B10-C31; A4-B10-C32; A4-B10-C33; A4-B10-C34;A4-B10-C35; A4-B10-C36; A4-B10-C37; A4-B10-C38; A4-B10-C39; A4-B10-C40;A4-B10-C41; A4-B10-C42; A4-B10-C43; A4-B10-C44; A4-B10-C45; A4-B10-C46;A5-B10-C1; A5-B10-C2; A5-B10-C3; A5-B10-C4; A5-B10-C5; A5-B10-C6;A5-B10-C7; A5-B10-C8; A5-B10-C9; A5-B10-C10; A5-B10-C11; A5-B10-C12;A5-B10-C13; A5-B10-C14; A5-B10-C15; A5-B10-C16; A5-B10-C17; A5-B10-C18;A5-B10-C19; A5-B10-C20; A5-B10-C21; A5-B10-C22; A5-B10-C23; A5-B10-C24;A5-B10-C25; A5-B10-C26; A5-B10-C27; A5-B10-C28; A5-B10-C29; A5-B10-C30;A5-B10-C31; A5-B10-C32; A5-B10-C33; A5-B10-C34; A5-B10-C35; A5-B10-C36;A5-B10-C37; A5-B10-C38; A5-B10-C39; A5-B10-C40; A5-B10-C41; A5-B10-C42;A5-B10-C43; A5-B10-C44; A5-B10-C45; A5-B10-C46; A6-B10-C1; A6-B10-C2;A6-B10-C3; A6-B10-C4; A6-B10-C5; A6-B10-C6; A6-B10-C7; A6-B10-C8;A6-B10-C9; A6-B10-C10; A6-B10-C11; A6-B10-C12; A6-B10-C13; A6-B10-C14;A6-B10-C15; A6-B10-C16; A6-B10-C17; A6-B10-C18; A6-B10-C19; A6-B10-C20;A6-B10-C21; A6-B10-C22; A6-B10-C23; A6-B10-C24; A6-B10-C25; A6-B10-C26;A6-B10-C27; A6-B10-C28; A6-B10-C29; A6-B10-C30; A6-B10-C31; A6-B10-C32;A6-B10-C33; A6-B10-C34; A6-B10-C35; A6-B10-C36; A6-B10-C37; A6-B10-C38;A6-B10-C39; A6-B10-C40; A6-B10-C41; A6-B10-C42; A6-B10-C43; A6-B10-C44;A6-B10-C45; A6-B10-C46; A7-B10-C1; A7-B10-C2; A7-B10-C3; A7-B10-C4;A7-B10-C5; A7-B10-C6; A7-B10-C7; A7-B10-C8; A7-B10-C9; A7-B10-C10;A7-B10-C11; A7-B10-C12; A7-B10-C13; A7-B10-C14; A7-B10-C15; A7-B10-C16;A7-B10-C17; A7-B10-C18; A7-B10-C19; A7-B10-C20; A7-B10-C21; A7-B10-C22;A7-B10-C23; A7-B10-C24; A7-B10-C25; A7-B10-C26; A7-B10-C27; A7-B10-C28;A7-B10-C29; A7-B10-C30; A7-B10-C31; A7-B10-C32; A7-B10-C33; A7-B10-C34;A7-B10-C35; A7-B10-C36; A7-B10-C37; A7-B10-C38; A7-B10-C39; A7-B10-C40;A7-B10-C41; A7-B10-C42; A7-B10-C43; A7-B10-C44; A7-B10-C45; A7-B10-C46;A8-B10-C1; A8-B10-C2; A8-B10-C3; A8-B10-C4; A8-B10-C5; A8-B10-C6;A8-B10-C7; A8-B10-C8; A8-B10-C9; A8-B10-C10; A8-B10-C11; A8-B10-C12;A8-B10-C13; A8-B10-C14; A8-B10-C15; A8-B10-C16; A8-B10-C17; A8-B10-C18;A8-B10-C19; A8-B10-C20; A8-B10-C21; A8-B10-C22; A8-B10-C23; A8-B10-C24;A8-B10-C25; A8-B10-C26; A8-B10-C27; A8-B10-C28; A8-B10-C29; A8-B10-C30;A8-B10-C31; A8-B10-C32; A8-B10-C33; A8-B10-C34; A8-B10-C35; A8-B10-C36;A8-B10-C37; A8-B10-C38; A8-B10-C39; A8-B10-C40; A8-B10-C41; A8-B10-C42;A8-B10-C43; A8-B10-C44; A8-B10-C45; A8-B10-C46; A9-B10-C1; A9-B10-C2;A9-B10-C3; A9-B10-C4; A9-B10-C5; A9-B10-C6; A9-B10-C7; A9-B10-C8;A9-B10-C9; A9-B10-C10; A9-B10-C11; A9-B10-C12; A9-B10-C13; A9-B10-C14;A9-B10-C15; A9-B10-C16; A9-B10-C17; A9-B10-C18; A9-B10-C19; A9-B10-C20;A9-B10-C21; A9-B10-C22; A9-B10-C23; A9-B10-C24; A9-B10-C25; A9-B10-C26;A9-B10-C27; A9-B10-C28; A9-B10-C29; A9-B10-C30; A9-B10-C31; A9-B10-C32;A9-B10-C33; A9-B10-C34; A9-B10-C35; A9-B10-C36; A9-B10-C37; A9-B10-C38;A9-B10-C39; A9-B10-C40; A9-B10-C41; A9-B10-C42; A9-B10-C43; A9-B10-C44;A9-B10-C45; A9-B10-C46; A10-B10-C1; A10-B10-C2; A10-B10-C3; A10-B10-C4;A10-B10-C5; A10-B10-C6; A10-B10-C7; A10-B10-C8; A10-B10-C9; A10-B10-C10;A10-B10-C11; A10-B10-C12; A10-B10-C13; A10-B10-C14; A10-B10-C15;A10-B10-C16; A10-B10-C17; A10-B10-C18; A10-B10-C19; A10-B10-C20;A10-B10-C21; A10-B10-C22; A10-B10-C23; A10-B10-C24; A10-B10-C25;A10-B10-C26; A10-B10-C27; A10-B10-C28; A10-B10-C29; A10-B10-C30;A10-B10-C31; A10-B10-C32; A10-B10-C33; A10-B10-C34; A10-B10-C35;A10-B10-C36; A10-B10-C37; A10-B10-C38; A10-B10-C39; A10-B10-C40;A10-B10-C41; A10-B10-C42; A10-B10-C43; A10-B10-C44; A10-B10-C45;A10-B10-C46; A11-B10-C1; A11-B10-C2; A11-B10-C3; A11-B10-C4; A11-B10-C5;A11-B10-C6; A11-B10-C7; A11-B10-C8; A11-B10-C9; A11-B10-C10;A11-B10-C11; A11-B10-C12; A11-B10-C13; A11-B10-C14; A11-B10-C15;A11-B10-C16; A11-B10-C17; A11-B10-C18; A11-B10-C19; A11-B10-C20;A11-B10-C21; A11-B10-C22; A11-B10-C23; A11-B10-C24; A11-B10-C25;A11-B10-C26; A11-B10-C27; A11-B10-C28; A11-B10-C29; A11-B10-C30;A11-B10-C31; A11-B10-C32; A11-B10-C33; A11-B10-C34; A11-B10-C35;A11-B10-C36; A11-B10-C37; A11-B10-C38; A11-B10-C39; A11-B10-C40;A11-B10-C41; A11-B10-C42; A11-B10-C43; A11-B10-C44; A11-B10-C45;A11-B10-C46; A12-B10-C1; A12-B10-C2; A12-B10-C3; A12-B10-C4; A12-B10-C5;A12-B10-C6; A12-B10-C7; A12-B10-C8; A12-B10-C9; A12-B10-C10;A12-B10-C11; A12-B10-C12; A12-B10-C13; A12-B10-C14; A12-B10-C15;A12-B10-C16; A12-B10-C17; A12-B10-C18; A12-B10-C19; A12-B10-C20;A12-B10-C21; A12-B10-C22; A12-B10-C23; A12-B10-C24; A12-B10-C25;A12-B10-C26; A12-B10-C27; A12-B10-C28; A12-B10-C29; A12-B10-C30;A12-B10-C31; A12-B10-C32; A12-B10-C33; A12-B10-C34; A12-B10-C35;A12-B10-C36; A12-B10-C37; A12-B10-C38; A12-B10-C39; A12-B10-C40;A12-B10-C41; A12-B10-C42; A12-B10-C43; A12-B10-C44; A12-B10-C45;A12-B10-C46; A13-B10-C1; A13-B10-C2; A13-B10-C3; A13-B10-C4; A13-B10-C5;A13-B10-C6; A13-B10-C7; A13-B10-C8; A13-B10-C9; A13-B10-C10;A13-B10-C11; A13-B10-C12; A13-B10-C13; A13-B10-C14; A13-B10-C15;A13-B10-C16; A13-B10-C17; A13-B10-C18; A13-B10-C19; A13-B10-C20;A13-B10-C21; A13-B10-C22; A13-B10-C23; A13-B10-C24; A13-B10-C25;A13-B10-C26; A13-B10-C27; A13-B10-C28; A13-B10-C29; A13-B10-C30;A13-B10-C31; A13-B10-C32; A13-B10-C33; A13-B10-C34; A13-B10-C35;A13-B10-C36; A13-B10-C37; A13-B10-C38; A13-B10-C39; A13-B10-C40;A13-B10-C41; A13-B10-C42; A13-B10-C43; A13-B10-C44; A13-B10-C45;A13-B10-C46; A14-B10-C1; A14-B10-C2; A14-B10-C3; A14-B10-C4; A14-B10-C5;A14-B10-C6; A14-B10-C7; A14-B10-C8; A14-B10-C9; A14-B10-C10;A14-B10-C11; A14-B10-C12; A14-B10-C13; A14-B10-C14; A14-B10-C15;A14-B10-C16; A14-B10-C17; A14-B10-C18; A14-B10-C19; A14-B10-C20;A14-B10-C21; A14-B10-C22; A14-B10-C23; A14-B10-C24; A14-B10-C25;A14-B10-C26; A14-B10-C27; A14-B10-C28; A14-B10-C29; A14-B10-C30;A14-B10-C31; A14-B10-C32; A14-B10-C33; A14-B10-C34; A14-B10-C35;A14-B10-C36; A14-B10-C37; A14-B10-C38; A14-B10-C39; A14-B10-C40;A14-B10-C41; A14-B10-C42; A14-B10-C43; A14-B10-C44; A14-B10-C45;A14-B10-C46; A15-B10-C1; A15-B10-C2; A15-B10-C3; A15-B10-C4; A15-B10-C5;A15-B10-C6; A15-B10-C7; A15-B10-C8; A15-B10-C9; A15-B10-C10;A15-B10-C11; A15-B10-C12; A15-B10-C13; A15-B10-C14; A15-B10-C15;A15-B10-C16; A15-B10-C17; A15-B10-C18; A15-B10-C19; A15-B10-C20;A15-B10-C21; A15-B10-C22; A15-B10-C23; A15-B10-C24; A15-B10-C25;A15-B10-C26; A15-B10-C27; A15-B10-C28; A15-B10-C29; A15-B10-C30;A15-B10-C31; A15-B10-C32; A15-B10-C33; A15-B10-C34; A15-B10-C35;A15-B10-C36; A15-B10-C37; A15-B10-C38; A15-B10-C39; A15-B10-C40;A15-B10-C41; A15-B10-C42; A15-B10-C43; A15-B10-C44; A15-B10-C45;A15-B10-C46; A16-B10-C1; A16-B10-C2; A16-B10-C3; A16-B10-C4; A16-B10-C5;A16-B10-C6; A16-B10-C7; A16-B10-C8; A16-B10-C9; A16-B10-C10;A16-B10-C11; A16-B10-C12; A16-B10-C13; A16-B10-C14; A16-B10-C15;A16-B10-C16; A16-B10-C17; A16-B10-C18; A16-B10-C19; A16-B10-C20;A16-B10-C21; A16-B10-C22; A16-B10-C23; A16-B10-C24; A16-B10-C25;A16-B10-C26; A16-B10-C27; A16-B10-C28; A16-B10-C29; A16-B10-C30;A16-B10-C31; A16-B10-C32; A16-B10-C33; A16-B10-C34; A16-B10-C35;A16-B10-C36; A16-B10-C37; A16-B10-C38; A16-B10-C39; A16-B10-C40;A16-B10-C41; A16-B10-C42; A16-B10-C43; A16-B10-C44; A16-B10-C45;A16-B10-C46; A17-B10-C1; A17-B10-C2; A17-B10-C3; A17-B10-C4; A17-B10-C5;A17-B10-C6; A17-B10-C7; A17-B10-C8; A17-B10-C9; A17-B10-C10;A17-B10-C11; A17-B10-C12; A17-B10-C13; A17-B10-C14; A17-B10-C15;A17-B10-C16; A17-B10-C17; A17-B10-C18; A17-B10-C19; A17-B10-C20;A17-B10-C21; A17-B10-C22; A17-B10-C23; A17-B10-C24; A17-B10-C25;A17-B10-C26; A17-B10-C27; A17-B10-C28; A17-B10-C29; A17-B10-C30;A17-B10-C31; A17-B10-C32; A17-B10-C33; A17-B10-C34; A17-B10-C35;A17-B10-C36; A17-B10-C37; A17-B10-C38; A17-B10-C39; A17-B10-C40;A17-B10-C41; A17-B10-C42; A17-B10-C43; A17-B10-C44; A17-B10-C45;A17-B10-C46; A18-B10-C1; A18-B10-C2; A18-B10-C3; A18-B10-C4; A18-B10-C5;A18-B10-C6; A18-B10-C7; A18-B10-C8; A18-B10-C9; A18-B10-C10;A18-B10-C11; A18-B10-C12; A18-B10-C13; A18-B10-C14; A18-B10-C15;A18-B10-C16; A18-B10-C17; A18-B10-C18; A18-B10-C19; A18-B10-C20;A18-B10-C21; A18-B10-C22; A18-B10-C23; A18-B10-C24; A18-B10-C25;A18-B10-C26; A18-B10-C27; A18-B10-C28; A18-B10-C29; A18-B10-C30;A18-B10-C31; A18-B10-C32; A18-B10-C33; A18-B10-C34; A18-B10-C35;A18-B10-C36; A18-B10-C37; A18-B10-C38; A18-B10-C39; A18-B10-C40;A18-B10-C41; A18-B10-C42; A18-B10-C43; A18-B10-C44; A18-B10-C45;A18-B10-C46; A19-B10-C1; A19-B10-C2; A19-B10-C3; A19-B10-C4; A19-B10-C5;A19-B10-C6; A19-B10-C7; A19-B10-C8; A19-B10-C9; A19-B10-C10;A19-B10-C11; A19-B10-C12; A19-B10-C13; A19-B10-C14; A19-B10-C15;A19-B10-C16; A19-B10-C17; A19-B10-C18; A19-B10-C19; A19-B10-C20;A19-B10-C21; A19-B10-C22; A19-B10-C23; A19-B10-C24; A19-B10-C25;A19-B10-C26; A19-B10-C27; A19-B10-C28; A19-B10-C29; A19-B10-C30;A19-B10-C31; A19-B10-C32; A19-B10-C33; A19-B10-C34; A19-B10-C35;A19-B10-C36; A19-B10-C37; A19-B10-C38; A19-B10-C39; A19-B10-C40;A19-B10-C41; A19-B10-C42; A19-B10-C43; A19-B10-C44; A19-B10-C45;A19-B10-C46; A20-B10-C1; A20-B10-C2; A20-B10-C3; A20-B10-C4; A20-B10-C5;A20-B10-C6; A20-B10-C7; A20-B10-C8; A20-B10-C9; A20-B10-C10;A20-B10-C11; A20-B10-C12; A20-B10-C13; A20-B10-C14; A20-B10-C15;A20-B10-C16; A20-B10-C17; A20-B10-C18; A20-B10-C19; A20-B10-C20;A20-B10-C21; A20-B10-C22; A20-B10-C23; A20-B10-C24; A20-B10-C25;A20-B10-C26; A20-B10-C27; A20-B10-C28; A20-B10-C29; A20-B10-C30;A20-B10-C31; A20-B10-C32; A20-B10-C33; A20-B10-C34; A20-B10-C35;A20-B10-C36; A20-B10-C37; A20-B10-C38; A20-B10-C39; A20-B10-C40;A20-B10-C41; A20-B10-C42; A20-B10-C43; A20-B10-C44; A20-B10-C45;A20-B10-C46; A21-B10-C1; A21-B10-C2; A21-B10-C3; A21-B10-C4; A21-B10-C5;A21-B10-C6; A21-B10-C7; A21-B10-C8; A21-B10-C9; A21-B10-C10;A21-B10-C11; A21-B10-C12; A21-B10-C13; A21-B10-C14; A21-B10-C15;A21-B10-C16; A21-B10-C17; A21-B10-C18; A21-B10-C19; A21-B10-C20;A21-B10-C21; A21-B10-C22; A21-B10-C23; A21-B10-C24; A21-B10-C25;A21-B10-C26; A21-B10-C27; A21-B10-C28; A21-B10-C29; A21-B10-C30;A21-B10-C31; A21-B10-C32; A21-B10-C33; A21-B10-C34; A21-B10-C35;A21-B10-C36; A21-B10-C37; A21-B10-C38; A21-B10-C39; A21-B10-C40;A21-B10-C41; A21-B10-C42; A21-B10-C43; A21-B10-C44; A21-B10-C45;A21-B10-C46; A22-B10-C1; A22-B10-C2; A22-B10-C3; A22-B10-C4; A22-B10-C5;A22-B10-C6; A22-B10-C7; A22-B10-C8; A22-B10-C9; A22-B10-C10;A22-B10-C11; A22-B10-C12; A22-B10-C13; A22-B10-C14; A22-B10-C15;A22-B10-C16; A22-B10-C17; A22-B10-C18; A22-B10-C19; A22-B10-C20;A22-B10-C21; A22-B10-C22; A22-B10-C23; A22-B10-C24; A22-B10-C25;A22-B10-C26; A22-B10-C27; A22-B10-C28; A22-B10-C29; A22-B10-C30;A22-B10-C31; A22-B10-C32; A22-B10-C33; A22-B10-C34; A22-B10-C35;A22-B10-C36; A22-B10-C37; A22-B10-C38; A22-B10-C39; A22-B10-C40;A22-B10-C41; A22-B10-C42; A22-B10-C43; A22-B10-C44; A22-B10-C45;A22-B10-C46; A23-B10-C1; A23-B10-C2; A23-B10-C3; A23-B10-C4; A23-B10-C5;A23-B10-C6; A23-B10-C7; A23-B10-C8; A23-B10-C9; A23-B10-C10;A23-B10-C11; A23-B10-C12; A23-B10-C13; A23-B10-C14; A23-B10-C15;A23-B10-C16; A23-B10-C17; A23-B10-C18; A23-B10-C19; A23-B10-C20;A23-B10-C21; A23-B10-C22; A23-B10-C23; A23-B10-C24; A23-B10-C25;A23-B10-C26; A23-B10-C27; A23-B10-C28; A23-B10-C29; A23-B10-C30;A23-B10-C31; A23-B10-C32; A23-B10-C33; A23-B10-C34; A23-B10-C35;A23-B10-C36; A23-B10-C37; A23-B10-C38; A23-B10-C39; A23-B10-C40;A23-B10-C41; A23-B10-C42; A23-B10-C43; A23-B10-C44; A23-B10-C45;A23-B10-C46; A24-B10-C1; A24-B10-C2; A24-B10-C3; A24-B10-C4; A24-B10-C5;A24-B10-C6; A24-B10-C7; A24-B10-C8; A24-B10-C9; A24-B10-C10;A24-B10-C11; A24-B10-C12; A24-B10-C13; A24-B10-C14; A24-B10-C15;A24-B10-C16; A24-B10-C17; A24-B10-C18; A24-B10-C19; A24-B10-C20;A24-B10-C21; A24-B10-C22; A24-B10-C23; A24-B10-C24; A24-B10-C25;A24-B10-C26; A24-B10-C27; A24-B10-C28; A24-B10-C29; A24-B10-C30;A24-B10-C31; A24-B10-C32; A24-B10-C33; A24-B10-C34; A24-B10-C35;A24-B10-C36; A24-B10-C37; A24-B10-C38; A24-B10-C39; A24-B10-C40;A24-B10-C41; A24-B10-C42; A24-B10-C43; A24-B10-C44; A24-B10-C45;A24-B10-C46; A25-B10-C1; A25-B10-C2; A25-B10-C3; A25-B10-C4; A25-B10-C5;A25-B10-C6; A25-B10-C7; A25-B10-C8; A25-B10-C9; A25-B10-C10;A25-B10-C11; A25-B10-C12; A25-B10-C13; A25-B10-C14; A25-B10-C15;A25-B10-C16; A25-B10-C17; A25-B10-C18; A25-B10-C19; A25-B10-C20;A25-B10-C21; A25-B10-C22; A25-B10-C23; A25-B10-C24; A25-B10-C25;A25-B10-C26; A25-B10-C27; A25-B10-C28; A25-B10-C29; A25-B10-C30;A25-BIO-C31; A25-B10-C32; A25-B10-C33; A25-B10-C34; A25-B10-C35;A25-B10-C36; A25-B10-C37; A25-B10-C38; A25-B10-C39; A25-B10-C40;A25-B10-C41; A25-B10-C42; A25-B10-C43; A25-B10-C44; A25-B10-C45;A25-B10-C46; A26-B10-C1; A26-B10-C2; A26-B10-C3; A26-B10-C4; A26-B10-C5;A26-B10-C6; A26-B10-C7; A26-B10-C8; A26-B10-C9; A26-B10-C10;A26-B10-C11; A26-B10-C12; A26-B10-C13; A26-B10-C14; A26-B10-C15;A26-B10-C16; A26-B10-C17; A26-B10-C18; A26-B10-C19; A26-B10-C20;A26-B10-C21; A26-B10-C22; A26-B10-C23; A26-B10-C24; A26-B10-C25;A26-B10-C26; A26-B10-C27; A26-B10-C28; A26-B10-C29; A26-B10-C30;A26-B10-C31; A26-B10-C32; A26-B10-C33; A26-B10-C34; A26-B10-C35;A26-B10-C36; A26-B10-C37; A26-B10-C38; A26-B10-C39; A26-B10-C40;A26-B10-C41; A26-B10-C42; A26-B10-C43; A26-B10-C44; A26-B10-C45;A26-B10-C46; A27-B10.C1; A27-B10-C2; A27-B10-C3; A27-B10-C4; A27-B10-C5;A27-B10-C6; A27-B10-C7; A27-B10-C8; A27-B10-C9; A27-B10-C10;A27-B10-C11; A27-B10-C12; A27-B10-C13; A27-B10-C14; A27-B10-C15;A27-B10-C16; A27-B10-C17; A27-B10-C18; A27-B10-C19; A27-B10-C20;A27-B10-C21; A27-B10-C22; A27-B10-C23; A27-B10-C24; A27-B10-C25;A27-B10-C26; A27-B10-C27; A27-B10-C28; A27-B10-C29; A27-B10-C30;A27-B10-C31; A27-B10-C32; A27-B10-C33; A27-B10-C34; A27-B10-C35;A27-B10-C36; A27-B10-C37; A27-B10-C38; A27-B10-C39; A27-B10-C40;A27-B10-C41; A27-B10-C42; A27-B10-C43; A27-B10-C44; A27-B10-C45;A27-B10-C46; A28-B10-C1; A28-B10-C2; A28-B10-C3; A28-B10-C4; A28-B10-C5;A28-B10-C6; A28-B10-C7; A28-B10-C8; A28-B10-C9; A28-B10-C10;A28-B10-C11; A28-B10-C12; A28-B10-C13; A28-B10-C14; A28-B10-C15;A28-B10-C16; A28-B10-C17; A28-B10-C18; A28-B10-C19; A28-B10-C20;A28-B10-C21; A28-B10-C22; A28-B10-C23; A28-B10-C24; A28-B10-C25;A28-B10-C26; A28-B10-C27; A28-B10-C28; A28-B10-C29; A28-B10-C30;A28-B10-C31; A28-B10-C32; A28-B10-C33; A28-B10-C34; A28-B10-C35;A28-B10-C36; A28-B10-C37; A28-B10-C38; A28-B10-C39; A28-B10-C40;A28-B10-C41; A28-B10-C42; A28-B10-C43; A28-B10-C44; A28-B10-C45;A28-B10-C46; A1-B11-C1; A1-B11-C2; A1-B11-C3; A1-B11-C4; A1-B11-C5;A1-B11-C6; A1-B11-C7; A1-B11-C8; A1-B11-C9; A1-B11-C10; A1-B11-C11;A1-B11-C12; A1-B11-C13; A1-B11-C14; A1-B11-C15; A1-B11-C16; A1-B11-C17;A1-B11-C18; A1-B11-C19; A1-B11-C20; A1-B11-C21; A1-B11-C22; A1-B11-C23;A1-B11-C24; A1-B11-C25; A1-B11-C26; A1-B11-C27; A1-B11-C28; A1-B11-C29;A1-B11-C30; A1-B11-C31; A1-B11-C32; A1-B11-C33; A1-B11-C34; A1-B11-C35;A1-B11-C36; A1-B11-C37; A1-B11-C38; A1-B11-C39; A1-B11-C40; A1-B11-C41;A1-B11-C42; A1-B11-C43; A1-B11-C44; A1-B11-C45; A1-B11-C46; A2-B11-C1;A2-B11-C2; A2-B11-C3; A2-B11-C4; A2-B11-C5; A2-B11-C6; A2-B11-C7;A2-B11-C8; A2-B11-C9; A2-B11-C10; A2-B11-C11; A2-B11-C12; A2-B11-C13;A2-B11-C14; A2-B11-C15; A2-B11-C16; A2-B11-C17; A2-B11-C18; A2-B11-C19;A2-B11-C20; A2-B11-C21; A2-B11-C22; A2-B11-C23; A2-B11-C24; A2-B11-C25;A2-B11-C26; A2-B11-C27; A2-B11-C28; A2-B11-C29; A2-B11-C30; A2-B11-C31;A2-B11-C32; A2-B11-C33; A2-B11-C34; A2-B11-C35; A2-B11-C36; A2-B11-C37;A2-B11-C38; A2-B11-C39; A2-B11-C40; A2-B11-C41; A2-B11-C42; A2-B11-C43;A2-B11-C44; A2-B11-C45; A2-B11-C46; A3-B11-C1; A3-B11-C2; A3-B11-C3;A3-B11-C4; A3-B11-C5; A3-B11-C6; A3-B11-C7; A3-B11-C8; A3-B11-C9;A3-B11-C10; A3-B11-C11; A3-B11-C12; A3-B11-C13; A3-B11-C14; A3-B11-C15;A3-B11-C16; A3-B11-C17; A3-B11-C18; A3-B11-C19; A3-B11-C20; A3-B11-C21;A3-B11-C22; A3-B11-C23; A3-B11-C24; A3-B11-C25; A3-B11-C26; A3-B11-C27;A3-B11-C28; A3-B11-C29; A3-B11-C30; A3-B11-C31; A3-B11-C32; A3-B11-C33;A3-B11-C34; A3-B11-C35; A3-B11-C36; A3-B11-C37; A3-B11-C38; A3-B11-C39;A3-B11-C40; A3-B11-C41; A3-B11-C42; A3-B11-C43; A3-B11-C44; A3-B11-C45;A3-B11-C46; A4-B11-C1; A4-B11-C2; A4-B11-C3; A4-B11-C4; A4-B11-C5;A4-B11-C6; A4-B11-C7; A4-B11-C8; A4-B11-C9; A4-B11-C10; A4-B11-C11;A4-B11-C12; A4-B11-C13; A4-B11-C14; A4-B11-C15; A4-B11-C16; A4-B11-C17;A4-B11-C18; A4-B11-C19; A4-B11-C20; A4-B11-C21; A4-B11-C22; A4-B11-C23;A4-B11-C24; A4-BH-C25; A4-B11-C26; A4-B11-C27; A4-B11-C28; A4-B11-C29;A4-B11-C30; A4-B11-C31; A4-B11-C32; A4-B11-C33; A4-B11-C34; A4-B11-C35;A4-B11-C36; A4-B11-C37; A4-B11-C38; A4-B11-C39; A4-B11-C40; A4-B11-C41;A4-B11-C42; A4-B11-C43; A4-B11-C44; A4-B11-C45; A4-B11-C46; A5-B11-C1;A5-B11-C2; A5-B11-C3; A5-B11-C4; A5-B11-C5; A5-B11-C6; A5-B11-C7;A5-B11-C8; A5-B11-C9; A5-B11-C10; A5-B11-C11; A5-B11-C12; A5-B11-C13;A5-B11-C14; A5-B11-C15; A5-B11-C16; A5-B11-C17; A5-B11-C18; A5-B11-C19;A5-B11-C20; A5-B11-C21; A5-B11-C22; A5-B11-C23; A5-B11-C24; A5-B11-C25;A5-B11-C26; A5-B11-C27; A5-B11-C28; A5-B11-C29; A5-B11-C30; A5-B11-C31;A5-B11-C32; A5-B11-C33; A5-B11-C34; A5-B11-C35; A5-B11-C36; A5-B11-C37;A5-B11-C38; A5-B11-C39; A5-B11-C40; A5-B11-C41; A5-B11-C42; A5-B11-C43;A5-B11-C44; A5-B11-C45; A5-B11-C46; A6-B11-C1; A6-B11-C2; A6-B11-C3;A6-B11-C4; A6-B11-C5; A6-B11-C6; A6-B11-C7; A6-B11-C8; A6-B11-C9;A6-B11-C10; A6-B11-C11; A6-B11-C12; A6-B11-C13; A6-B11-C14; A6-B11-C15;A6-B11-C16; A6-B11-C17; A6-B11-C18; A6-B11-C19; A6-B11-C20; A6-B11-C21;A6-B11-C22; A6-B11-C23; A6-B11-C24; A6-B11-C25; A6-B11-C26; A6-B11-C27;A6-B11-C28; A6-B11-C29; A6-B11-C30; A6-B11-C31; A6-B11-C32; A6-B11-C33;A6-B11-C34; A6-B11-C35; A6-B11-C36; A6-B11-C37; A6-B11-C38; A6-B11-C39;A6-B11-C40; A6-B11-C41; A6-B11-C42; A6-B11-C43; A6-B11-C44; A6-B11-C45;A6-B11-C46; A7-B11-C1; A7-B11-C2; A7-B11-C3; A7-B11-C4; A7-B11-C5;A7-B11-C6; A7-B11-C7; A7-B11-C8; A7-B11-C9; A7-B11-C10; A7-B11-C11;A7-B11-C12; A7-B11-C13; A7-B11-C14; A7-B11-C15; A7-B11-C16; A7-B11-C17;A7-B11-C18; A7-B11-C19; A7-B11-C20; A7-B11-C21; A7-B11-C22; A7-B11-C23;A7-B11-C24; A7-B11-C25; A7-B11-C26; A7-B11-C27; A7-B11-C28; A7-B11-C29;A7-B11-C30; A7-B11-C31; A7-B11-C32; A7-B11-C33; A7-B11-C34; A7-B11-C35;A7-B11-C36; A7-B11-C37; A7-B11-C38; A7-B11-C39; A7-B11-C40; A7-B11-C41;A7-B11-C42; A7-B11-C43; A7-B11-C44; A7-B11-C45; A7-B11-C46; A8-B11-C1;A8-B11-C2; A8-B11-C3; A8-B11-C4; A8-B11-C5; A8-B11-C6; A8-B11-C7;A8-B11-C8; A8-B11-C9; A8-B11-C10; A8-B11-C11; A8-B11-C12; A8-B11-C13;A8-B11-C14; A8-B11-C15; A8-B11-C16; A8-B11-C17; A8-B11-C18; A8-B11-C19;A8-B11-C20; A8-B11-C21; A8-B11-C22; A8-B11-C23; A8-B11-C24; A8-B11-C25;A8-B11-C26; A8-B11-C27; A8-B11-C28; A8-B11-C29; A8-B11-C30; A8-B11-C31;A8-B11-C32; A8-B11-C33; A8-B11-C34; A8-B11-C35; A8-B11-C36; A8-B11-C37;A8-B11-C38; A8-B11-C39; A8-B11-C40; A8-B11-C41; A8-B11-C42; A8-B11-C43;A8-B11-C44; A8-B11-C45; A8-B11-C46; A9-B11-C1; A9-B11-C2; A9-B11-C3;A9-B11-C4; A9-B11-C5; A9-B11-C6; A9-B11-C7; A9-B11-C8; A9-B11-C9;A9-B11-C10; A9-B11-C11; A9-B11-C12; A9-B11-C13; A9-B11-C14; A9-B11-C15;A9-B11-C16; A9-B11-C17; A9-B11-C18; A9-B11-C19; A9-B11-C20; A9-B11-C21;A9-B11-C22; A9-B11-C23; A9-B11-C24; A9-B11-C25; A9-B11-C26; A9-B11-C27;A9-B11-C28; A9-B11-C29; A9-B11-C30; A9-B11-C31; A9-B11-C32; A9-B11-C33;A9-B11-C34; A9-B11-C35; A9-B11-C36; A9-B11-C37; A9-B11-C38; A9-B11-C39;A9-B11-C40; A9-B11-C41; A9-B11-C42; A9-B11-C43; A9-B11-C44; A9-B11-C45;A9-B11-C46; A10-B11-C1; A10-B11-C2; A10-B11-C3; A10-B11-C4; A10-B11-C5;A10-B11-C6; A10-B11-C7; A10-B11-C8; A10-B11-C9; A10-B11-C10;A10-B11-C11; A10-B11-C12; A10-B11-C13; A10-B11-C14; A10-B11-C15;A10-B11-C16; A10-B11-C17; A10-B11-C18; A10-B11-C19; A10-B11-C20;A10-B11-C21; A10-B11-C22; A10-B11-C23; A10-B11-C24; A10-B11-C25;A10-B11-C26; A10-B11-C27; A10-B11-C28; A10-B11-C29; A10-B11-C30;A10-B11-C31; A10-B11-C32; A10-B11-C33; A10-B11-C34; A10-B11-C35;A10-B11-C36; A10-B11-C37; A10-B11-C38; A10-B11-C39; A10-B11-C40;A10-B11-C41; A10-B11-C42; A10-B11-C43; A10-B11-C44; A10-B11-C45;A10-B11-C46; A11-B11-C1; A11-B11-C2; A11-B11-C3; A11-B11-C4; A11-B11-C5;A11-B11-C6; A11-B11-C7; A11-B11-C8; A11-B11-C9; A11-B11-C10;A11-B11-C11; A11-B11-C12; A11-B11-C13; A11-B11-C14; A11-B11-C15;A11-B11-C16; A11-B11-C17; A11-B11-C18; A11-B11-C19; A11-B11-C20;A11-B11-C21; A11-B11-C22; A11-B11-C23; A11-B11-C24; A11-B11-C25;A11-B11-C26; A11-B11-C27; A11-B11-C28; A11-B11-C29; A11-B11-C30;A11-B11-C31; A11-B11-C32; A11-B11-C33; A11-B11-C34; A11-B11-C35;A11-B11-C36; A11-B11-C37; A11-B11-C38; A11-B11-C39; A11-B11-C40;A11-B11-C41; A11-B11-C42; A11-B11-C43; A11-B11-C44; A11-B11-C45;A11-B11-C46; A12-B11-C1; A12-B11-C2; A12-B11-C3; A12-B11-C4; A12-B11-C5;A12-B11-C6; A12-B11-C7; A12-B11-C8; A12-B11-C9; A12-B11-C10;A12-B11-C11; A12-B11-C12; A12-B11-C13; A12-B11-C14; A12-B11-C15;A12-B11-C16; A12-B11-C17; A12-B11-C18; A12-B11-C19; A12-B11-C20;A12-B11-C21; A12-B11-C22; A12-B11-C23; A12-B11-C24; A12-B11-C25;A12-B11-C26; A12-B11-C27; A12-B11-C28; A12-B11-C29; A12-B11-C30;A12-B11-C31; A12-B11-C32; A12-B11-C33; A12-B11-C34; A12-B11-C35;A12-B11-C36; A12-B11-C37; A12-B11-C38; A12-B11-C39; A12-B11-C40;A12-B11-C41; A12-B11-C42; A12-B11-C43; A12-B11-C44; A12-B11-C45;A12-B11-C46; A13-B11-C1; A13-B11-C2; A13-B11-C3; A13-B11-C4; A13-B11-C5;A13-B11-C6; A13-B11-C7; A13-B11-C8; A13-B11-C9; A13-B11-C10;A13-B11-C11; A13-B11-C12; A13-B11-C13; A13-B11-C14; A13-B11-C15;A13-B11-C16; A13-B11-C17; A13-B11-C18; A13-B11-C19; A13-B11-C20;A13-B11-C21; A13-B11-C22; A13-B11-C23; A13-B11-C24; A13-B11-C25;A13-B11-C26; A13-B11-C27; A13-B11-C28; A13-B11-C29; A13-B11-C30;A13-B11-C31; A13-B11-C32; A13-B11-C33; A13-B11-C34; A13-B11-C35;A13-B11-C36; A13-B11-C37; A13-B11-C38; A13-B11-C39; A13-B11-C40;A13-B11-C41; A13-B11-C42; A13-B11-C43; A13-B11-C44; A13-B11-C45;A13-B11-C46; A14-B11-C1; A14-B11-C2; A14-B11-C3; A14-B11-C4; A14-B11-C5;A14-B11-C6; A14-B11-C7; A14-B11-C8; A14-B11-C9; A14-B11-C10;A14-B11-C11; A14-B11-C12; A14-B11-C13; A14-B11-C14; A14-B11-C15;A14-B11-C16; A14-B11-C17; A14-B11-C18; A14-B11-C19; A14-B11-C20;A14-B11-C21; A14-B11-C22; A14-B11-C23; A14-B11-C24; A14-B11-C25;A14-B11-C26; A14-B11-C27; A14-B11-C28; A14-B11-C29; A14-B11-C30;A14-B11-C31; A14-B11-C32; A14-B11-C33; A14-B11-C34; A14-B11-C35;A14-B11-C36; A14-B11-C37; A14-B11-C38; A14-B11-C39; A14-B11-C40;A14-B11-C41; A14-B11-C42; A14-B11-C43; A14-B11-C44; A14-B11-C45;A14-B11-C46; A15-B11-C1; A15-B11-C2; A15-B11-C3; A15-B11-C4; A15-B11-C5;A15-B11-C6; A15-B11-C7; A15-B11-C8; A15-B11-C9; A15-B11-C10;A15-B11-C11; A15-B11-C12; A15-B11-C13; A15-B11-C14; A15-B11-C15;A15-B11-C16; A15-B11-C17; A15-B11-C18; A15-B11-C19; A15-B11-C20;A15-B11-C21; A15-B11-C22; A15-B11-C23; A15-B11-C24; A15-B11-C25;A15-B11-C26; A15-B11-C27; A15-B11-C28; A15-B11-C29; A15-B11-C30;A15-B11-C31; A15-B11-C32; A15-B11-C33; A15-B11-C34; A15-B11-C35;A15-B11-C36; A15-B11-C37; A15-B11-C38; A15-B11-C39; A15-B11-C40;A15-B11-C41; A15-B11-C42; A15-B11-C43; A15-B11-C44; A15-B11-C45;A15-B11-C46; A16-B11-C1; A16-B11-C2; A16-B11-C3; A16-B11-C4; A16-B11-C5;A16-B11-C6; A16-B11-C7; A16-B11-C8; A16-B11-C9; A16-B11-C10;A16-B11-C11; A16-B11-C12; A16-B11-C13; A16-B11-C14; A16-B11-C15;A16-B11-C16; A16-B11-C17; A16-B11-C18; A16-B11-C19; A16-B11-C20;A16-B11-C21; A16-B11-C22; A16-B11-C23; A16-B11-C24; A16-B11-C25;A16-B11-C26; A16-B11-C27; A16-B11-C28; A16-B11-C29; A16-B11-C30;A16-B11-C31; A16-B11-C32; A16-B11-C33; A16-B11-C34; A16-B11-C35;A16-B11-C36; A16-B11-C37; A16-B11-C38; A16-B11-C39; A16-B11-C40;A16-B11-C41; A16-B11-C42; A16-B11-C43; A16-B11-C44; A16-B11-C45;A16-B11-C46; A17-B11-C1; A17-B11-C2; A17-B11-C3; A17-B11-C4; A17-B11-C5;A17-B11-C6; A17-B11-C7; A17-B11-C8; A17-B11-C9; A17-B11-C10;A17-B11-C11; A17-B11-C12; A17-B11-C13; A17-B11-C14; A17-B11-C15;A17-B11-C16; A17-B11-C17; A17-B11-C18; A17-B11-C19; A17-B11-C20;A17-B11-C21; A17-B11-C22; A17-B11-C23; A17-B11-C24; A17-B11-C25;A17-B11-C26; A17-B11-C27; A17-B11-C28; A17-B11-C29; A17-B11-C30;A17-B11-C31; A17-B11-C32; A17-B11-C33; A17-B11-C34; A17-B11-C35;A17-B11-C36; A17-B11-C37; A17-B11-C38; A17-B11-C39; A17-B11-C40;A17-B11-C41; A17-B11-C42; A17-B11-C43; A17-B11-C44; A17-B11-C45;A17-B11-C46; A18-B11-C1; A18-B11-C2; A18-B11-C3; A18-B11-C4; A18-B11-C5;A18-B11-C6; A18-B11-C7; A18-B11-C8; A18-B11-C9; A18-B11-C10;A18-B11-C11; A18-B11-C12; A18-B11-C13; A18-B11-C14; A18-B11-C15;A18-B11-C16; A18-B11-C17; A18-B11-C18; A18-B11-C19; A18-B11-C20;A18-B11-C21; A18-B11-C22; A18-B11-C23; A18-B11-C24; A18-B11-C25;A18-B11-C26; A18-B11-C27; A18-B11-C28; A18-B11-C29; A18-B11-C30;A18-B11-C31; A18-B11-C32; A18-B11-C33; A18-B11-C34; A18-B11-C35;A18-B11-C36; A18-B11-C37; A18-B11-C38; A18-B11-C39; A18-B11-C40;A18-B11-C41; A18-B11-C42; A18-B11-C43; A18-B11-C44; A18-B11-C45;A18-B11-C46; A19-B11-C1; A19-B11-C2; A19-B11-C3; A19-B11-C4; A19-B11-C5;A19-B11-C6; A19-B11-C7; A19-B11-C8; A19-B11-C9; A19-B11-C10;A19-B11-C11; A19-B11-C12; A19-B11-C13; A19-B11-C14; A19-B11-C15;A19-B11-C16; A19-B11-C17; A19-B11-C18; A19-B11-C19; A19-B11-C20;A19-B11-C21; A19-B11-C22; A19-B11-C23; A19-B11-C24; A19-B11-C25;A19-B11-C26; A19-B11-C27; A19-B11-C28; A19-B11-C29; A19-B11-C30;A19-B11-C31; A19-B11-C32; A19-B11-C33; A19-B11-C34; A19-B11-C35;A19-B11-C36; A19-B11-C37; A19-B11-C38; A19-B11-C39; A19-B11-C40;A19-B11-C41; A19-B11-C42; A19-B11-C43; A19-B11-C44; A19-B11-C45;A19-B11-C46; A20-B11-C1; A20-B11-C2; A20-B11-C3; A20-B11-C4; A20-B11-C5;A20-B11-C6; A20-B11-C7; A20-B11-C8; A20-B11-C9; A20-B11-C10;A20-B11-C11; A20-B11-C12; A20-B11-C13; A20-B11-C14; A20-B11-C15;A20-B11-C16; A20-B11-C17; A20-B11-C18; A20-B11-C19; A20-B11-C20;A20-B11-C21; A20-B11-C22; A20-B11-C23; A20-B11-C24; A20-B11-C25;A20-B11-C26; A20-B11-C27; A20-B11-C28; A20-B11-C29; A20-B11-C30;A20-B11-C31; A20-B11-C32; A20-B11-C33; A20-B11-C34; A20-B11-C35;A20-B11-C36; A20-B11-C37; A20-B11-C38; A20-B11-C39; A20-B11-C40;A20-B11-C41; A20-B11-C42; A20-B11-C43; A20-B11-C44; A20-B11-C45;A20-B11-C46; A21-B11-C1; A21-B11-C2; A21-B11-C3; A21-B11-C4; A21-B11-C5;A21-B11-C6; A21-B11-C7; A21-B11-C8; A21-B11-C9; A21-B11-C10;A21-B11-C11; A21-B11-C12; A21-B11-C13; A21-B11-C14; A21-B11-C15;A21-B11-C16; A21-B11-C17; A21-B11-C18; A21-B11-C19; A21-B11-C20;A21-B11-C21; A21-B11-C22; A21-B11-C23; A21-B11-C24; A21-B11-C25;A21-B11-C26; A21-B11-C27; A21-B11-C28; A21-B11-C29; A21-B11-C30;A21-B11-C31; A21-B11-C32; A21-B11-C33; A21-B11-C34; A21-B11-C35;A21-B11-C36; A21-B11-C37; A21-B11-C38; A21-B11-C39; A21-B11-C40;A21-B11-C41; A21-B11-C42; A21-B11-C43; A21-B11-C44; A21-B11-C45;A21-B11-C46; A22-B11-C1; A22-B11-C2; A22-B11-C3; A22-B11-C4; A22-B11-C5;A22-B11-C6; A22-B11-C7; A22-B11-C8; A22-B11-C9; A22-B11-C10;A22-B11-C11; A22-B11-C12; A22-B11-C13; A22-B11-C14; A22-B11-C15;A22-B11-C16; A22-B11-C17; A22-B11-C18; A22-B11-C19; A22-B11-C20;A22-B11-C21; A22-B11-C22; A22-B11-C23; A22-B11-C24; A22-B11-C25;A22-B11-C26; A22-B11-C27; A22-B11-C28; A22-B11-C29; A22-B11-C30;A22-B11-C31; A22-B11-C32; A22-B11-C33; A22-B11-C34; A22-B11-C35;A22-B11-C36; A22-B11-C37; A22-B11-C38; A22-B11-C39; A22-B11-C40;A22-B11-C41; A22-B11-C42; A22-B11-C43; A22-B11-C44; A22-B11-C45;A22-B11-C46; A23-B11-C1; A23-B11-C2; A23-B11-C3; A23-B11-C4; A23-B11-C5;A23-B11-C6; A23-B11-C7; A23-B11-C8; A23-B11-C9; A23-B11-C10;A23-B11-C11; A23-B11-C12; A23-B11-C13; A23-B11-C14; A23-B11-C15;A23-B11-C16; A23-B11-C17; A23-B11-C18; A23-B11-C19; A23-B11-C20;A23-B11-C21; A23-B11-C22; A23-B11-C23; A23-B11-C24; A23-B11-C25;A23-B11-C26; A23-B11-C27; A23-B11-C28; A23-B11-C29; A23-B11-C30;A23-B11-C31; A23-B11-C32; A23-B11-C33; A23-B11-C34; A23-B11-C35;A23-B11-C36; A23-B11-C37; A23-B11-C38; A23-B11-C39; A23-B11-C40;A23-B11-C41; A23-B11-C42; A23-B11-C43; A23-B11-C44; A23-B11-C45;A23-B11-C46; A24-B11-C1; A24-B11-C2; A24-B11-C3; A24-B11-C4; A24-B11-C5;A24-B11-C6; A24-B11-C7; A24-B11-C8; A24-B11-C9; A24-B11-C10;A24-B11-C11; A24-B11-C12; A24-B11-C13; A24-B11-C14; A24-B11-C15;A24-B11-C16; A24-B11-C17; A24-B11-C18; A24-B11-C19; A24-B11-C20;A24-B11-C21; A24-B11-C22; A24-B11-C23; A24-B11-C24; A24-B11-C25;A24-B11-C26; A24-B11-C27; A24-B11-C28; A24-B11-C29; A24-B11-C30;A24-B11-C31; A24-B11-C32; A24-B11-C33; A24-B11-C34; A24-B11-C35;A24-B11-C36; A24-B11-C37; A24-B11-C38; A24-B11-C39; A24-B11-C40;A24-B11-C41; A24-B11-C42; A24-B11-C43; A24-B11-C44; A24-B11-C45;A24-B11-C46; A25-B11-C1; A25-B11-C2; A25-B11-C3; A25-B11-C4; A25-B11-C5;A25-B11-C6; A25-B11-C7; A25-B11-C8; A25-B11-C9; A25-B11-C10;A25-B11-C11; A25-B11-C12; A25-B11-C13; A25-B11-C14; A25-B11-C15;A25-B11-C16; A25-B11-C17; A25-B11-C18; A25-B11-C19; A25-B11-C20;A25-B11-C21; A25-B11-C22; A25-B11-C23; A25-B11-C24; A25-B11-C25;A25-B11-C26; A25-B11-C27; A25-B11-C28; A25-B11-C29; A25-B11-C30;A25-B11-C31; A25-B11-C32; A25-B11-C33; A25-B11-C34; A25-B11-C35;A25-B11-C36; A25-B11-C37; A25-B11-C38; A25-B11-C39; A25-B11-C40;A25-B11-C41; A25-B11-C42; A25-B11-C43; A25-B11-C44; A25-B11-C45;A25-B11-C46; A26-B11-C1; A26-B11-C2; A26-B11-C3; A26-B11-C4; A26-B11-C5;A26-B11-C6; A26-B11-C7; A26-B11-C8; A26-B11-C9; A26-B11-C10;A26-B11-C11; A26-B11-C12; A26-B11-C13; A26-B11-C14; A26-B11-C15;A26-B11-C16; A26-B11-C17; A26-B11-C18; A26-B11-C19; A26-B11-C20;A26-B11-C21; A26-B11-C22; A26-B11-C23; A26-B11-C24; A26-B11-C25;A26-B11-C26; A26-B11-C27; A26-B11-C28; A26-B11-C29; A26-B11-C30;A26-B11-C31; A26-B11-C32; A26-B11-C33; A26-B11-C34; A26-B11-C35;A26-B11-C36; A26-B11-C37; A26-B11-C38; A26-B11-C39; A26-B11-C40;A26-B11-C41; A26-B11-C42; A26-B11-C43; A26-B11-C44; A26-B11-C45;A26-B11-C46; A27-B11-C1; A27-B11-C2; A27-B11-C3; A27-B11-C4; A27-B11-C5;A27-B11-C6; A27-B11-C7; A27-B11-C8; A27-B11-C9; A27-B11-C10;A27-B11-C11; A27-B11-C12; A27-B11-C13; A27-B11-C14; A27-B11-C15;A27-B11-C16; A27-B11-C17; A27-B11-C18; A27-B11-C19; A27-B11-C20;A27-B11-C21; A27-B11-C22; A27-B11-C23; A27-B11-C24; A27-B11-C25;A27-B11-C26; A27-B11-C27; A27-B11-C28; A27-B11-C29; A27-B11-C30;A27-B11-C31; A27-B11-C32; A27-B11-C33; A27-B11-C34; A27-B11-C35;A27-B11-C36; A27-B11-C37; A27-B11-C38; A27-B11-C39; A27-B11-C40;A27-B11-C41; A27-B11-C42; A27-B11-C43; A27-B11-C44; A27-B11-C45;A27-B11-C46; A28-B11-C1; A28-B11-C2; A28-B11-C3; A28-B11-C4; A28-B11-C5;A28-B11-C6; A28-B11-C7; A28-B11-C8; A28-B11-C9; A28-B11-C10;A28-B11-C11; A28-B11-C12; A28-B11-C13; A28-B11-C14; A28-B11-C15;A28-B11-C16; A28-B11-C17; A28-B11-C18; A28-B11-C19; A28-B11-C20;A28-B11-C21; A28-B11-C22; A28-B11-C23; A28-B11-C24; A28-B11-C25;A28-B11-C26; A28-B11-C27; A28-B11-C28; A28-B11-C29; A28-B11-C30;A28-B11-C31; A28-B11-C32; A28-B11-C33; A28-B11-C34; A28-B11-C35;A28-B11-C36; A28-B11-C37; A28-B11-C38; A28-B11-C39; A28-B11-C40;A28-B11-C41; A28-B11-C42; A28-B11-C43; A28-B11-C44; A28-B11-C45;A28-B11-C46; A1-B12-C1; A1-B12-C2; A1-B12-C3; A1-B12-C4; A1-B12-C5;A1-B12-C6; A1-B12-C7; A1-B12-C8; A1-B12-C9; A1-B12-C10; A1-B12-C11;A1-B12-C12; A1-B12-C13; A1-B12-C14; A1-B12-C15; A1-B12-C16; A1-B12-C17;A1-B12-C18; A1-B12-C19; A1-B12-C20; A1-B12-C21; A1-B12-C22; A1-B12-C23;A1-B12-C24; A1-B12-C25; A1-B12-C26; A1-B12-C27; A1-B12-C28; A1-B12-C29;A1-B12-C30; A1-B12-C31; A1-B12-C32; A1-B12-C33; A1-B12-C34; A1-B12-C35;A1-B12-C36; A1-B12-C37; A1-B12-C38; A1-B12-C39; A1-B12-C40; A1-B12-C41;A1-B12-C42; A1-B12-C43; A1-B12-C44; A1-B12-C45; A1-B12-C46; A2-B12-C1;A2-B12-C2; A2-B12-C3; A2-B12-C4; A2-B12-C5; A2-B12-C6; A2-B12-C7;A2-B12-C8; A2-B12-C9; A2-B12-C10; A2-B12-C11; A2-B12-C12; A2-B12-C13;A2-B12-C14; A2-B12-C15; A2-B12-C16; A2-B12-C17; A2-B12-C18; A2-B12-C19;A2-B12-C20; A2-B12-C21; A2-B12-C22; A2-B12-C23; A2-B12-C24; A2-B12-C25;A2-B12-C26; A2-B12-C27; A2-B12-C28; A2-B12-C29; A2-B12-C30; A2-B12-C31;A2-B12-C32; A2-B12-C33; A2-B12-C34; A2-B12-C35; A2-B12-C36; A2-B12-C37;A2-B12-C38; A2-B12-C39; A2-B12-C40; A2-B12-C41; A2-B12-C42; A2-B12-C43;A2-B12-C44; A2-B12-C45; A2-B12-C46; A3-B12-C1; A3-B12-C2; A3-B12-C3;A3-B12-C4; A3-B12-C5; A3-B12-C6; A3-B12-C7; A3-B12-C8; A3-B12-C9;A3-B12-C10; A3-B12-C11; A3-B12-C12; A3-B12-C13; A3-B12-C14; A3-B12-C15;A3-B12-C16; A3-B12-C17; A3-B12-C18; A3-B12-C19; A3-B12-C20; A3-B12-C21;A3-B12-C22; A3-B12-C23; A3-B12-C24; A3-B12-C25; A3-B12-C26; A3-B12-C27;A3-B12-C28; A3-B12-C29; A3-B12-C30; A3-B12-C31; A3-B12-C32; A3-B12-C33;A3-B12-C34; A3-B12-C35; A3-B12-C36; A3-B12-C37; A3-B12-C38; A3-BI2-C39;A3-B12-C40; A3-B12-C41; A3-B12-C42; A3-B12-C43; A3-B12-C44; A3-B12-C45;A3-B12-C46; A4-B12-C1; A4-B12-C2; A4-B12-C3; A4-B12-C4; A4-B12-C5;A4-B12-C6; A4-B12-C7; A4-B12-C8; A4-B12-C9; A4-B12-C10; A4-B12-C11;A4-B12-C12; A4-B12-C13; A4-B12-C14; A4-B12-C15; A4-B12-C16; A4-B12-C17;A4-B12-C18; A4-B12-C19; A4-B12-C20; A4-B12-C21; A4-B12-C22; A4-B12-C23;A4-B12-C24; A4-B12-C25; A4-B12-C26; A4-B12-C27; A4-B12-C28; A4-B12-C29;A4-B12-C30; A4-B12-C31; A4-B12-C32; A4-B12-C33; A4-B12-C34; A4-B12-C35;A4-B12-C36; A4-B12-C37; A4-B12-C38; A4-B12-C39; A4-B12-C40; A4-B12-C41;A4-B12-C42; A4-B12-C43; A4-B12-C44; A4-B12-C45; A4-B12-C46; A5-B12-C1;A5-B12-C2; A5-B12-C3; A5-B12-C4; A5-B12-C5; A5-B12-C6; A5-B12-C7;A5-B12-C8; A5-B12-C9; A5-B12-C10; A5-B12-C11; A5-B12-C12; A5-B12-C13;A5-B12-C14; A5-B12-C15; A5-B12-C16; A5-B12-C17; A5-B12-C18; A5-B12-C19;A5-B12-C20; A5-B12-C21; A5-B12-C22; A5-B12-C23; A5-B12-C24; A5-B12-C25;A5-B12-C26; A5-B12-C27; A5-B12-C28; A5-B12-C29; A5-B12-C30; A5-B12-C31;A5-B12-C32; A5-B12-C33; A5-B12-C34; A5-B12-C35; A5-B12-C36; A5-B12-C37;A5-B12-C38; A5-B12-C39; A5-B12-C40; A5-B12-C41; A5-B12-C42; A5-B12-C43;A5-B12-C44; A5-B12-C45; A5-B12-C46; A6-B12-C1; A6-B12-C2; A6-B12-C3;A6-B12-C4; A6-B12-C5; A6-B12-C6; A6-B12-C7; A6-B12-C8; A6-B12-C9;A6-B12-C10; A6-B12-C11; A6-B12-C12; A6-B12-C13; A6-B12-C14; A6-B12-C15;A6-B12-C16; A6-B12-C17; A6-B12-C18; A6-B12-C19; A6-B12-C20; A6-B12-C21;A6-B12-C22; A6-B12-C23; A6-B12-C24; A6-B12-C25; A6-B12-C26; A6-B12-C27;A6-B12-C28; A6-B12-C29; A6-B12-C30; A6-B12-C31; A6-B12-C32; A6-B12-C33;A6-B12-C34; A6-B12-C35; A6-B12-C36; A6-B12-C37; A6-B12-C38; A6-B12-C39;A6-B12-C40; A6-B12-C41; A6-B12-C42; A6-B12-C43; A6-B12-C44; A6-B12-C45;A6-B12-C46; A7-B12-C1; A7-B12-C2; A7-B12-C3; A7-B12-C4; A7-B12-C5;A7-B12-C6; A7-B12-C7; A7-B12-C8; A7-B12-C9; A7-B12-C10; A7-B12-C11;A7-B12-C12; A7-B12-C13; A7-B12-C14; A7-B12-C15; A7-B12-C16; A7-B12-C17;A7-B12-C18; A7-B12-C19; A7-B12-C20; A7-B12-C21; A7-B12-C22; A7-B12-C23;A7-B12-C24; A7-B12-C25; A7-B12-C26; A7-B12-C27; A7-B12-C28; A7-B12-C29;A7-B12-C30; A7-B12-C31; A7-B12-C32; A7-B12-C33; A7-B12-C34; A7-B12-C35;A7-B12-C36; A7-B12-C37; A7-B12-C38; A7-B12-C39; A7-B12-C40; A7-B12-C41;A7-B12-C42; A7-B12-C43; A7-B12-C44; A7-B12-C45; A7-B12-C46; A8-B12-C1;A8-B12-C2; A8-B12-C3; A8-B12-C4; A8-B12-C5; A8-B12-C6; A8-B12-C7;A8-B12-C8; A8-B12-C9; A8-B12-C10; A8-B12-C11; A8-B12-C12; A8-B12-C13;A8-B12-C14; A8-B12-C15; A8-B12-C16; A8-B12-C17; A8-B12-C18; A8-B12-C19;A8-B12-C20; A8-B12-C21; A8-B12-C22; A8-B12-C23; A8-B12-C24; A8-B12-C25;A8-B12-C26; A8-B12-C27; A8-B12-C28; A8-B12-C29; A8-B12-C30; A8-B12-C31;A8-B12-C32; A8-B12-C33; A8-B12-C34; A8-B12-C35; A8-B12-C36; A8-B12-C37;A8-B12-C38; A8-B12-C39; A8-B12-C40; A8-B12-C41; A8-B12-C42; A8-B12-C43;A8-B12-C44; A8-B12-C45; A8-B12-C46; A9-B12-C1; A9-B12-C2; A9-B12-C3;A9-B12-C4; A9-B12-C5; A9-B12-C6; A9-B12-C7; A9-B12-C8; A9-B12-C9;A9-B12-C10; A9-B12-C11; A9-B12-C12; A9-B12-C13; A9-B12-C14; A9-B12-C15;A9-B12-C16; A9-B12-C17; A9-B12-C18; A9-B12-C19; A9-B12-C20; A9-B12-C21;A9-B12-C22; A9-B12-C23; A9-B12-C24; A9-B12-C25; A9-B12-C26; A9-B12-C27;A9-B12-C28; A9-B12-C29; A9-B12-C30; A9-B12-C31; A9-B12-C32; A9-B12-C33;A9-B12-C34; A9-B12-C35; A9-B12-C36; A9-B12-C37; A9-B12-C38; A9-B12-C39;A9-B12-C40; A9-B12-C41; A9-B12-C42; A9-B12-C43; A9-B12-C44; A9-B12-C45;A9-B12-C46; A10-B12-C1; A10-B12-C2; A10-B12-C3; A10-B12-C4; A10-B12-C5;A10-B12-C6; A10-B12-C7; A10-B12-C8; A10-B12-C9; A10-B12-C10;A10-B12-C11; A10-B12-C12; A10-B12-C13; A10-B12-C14; A10-B12-C15;A10-B12-C16; A10-B12-C17; A10-B12-C18; A10-B12-C19; A10-B12-C20;A10-B12-C21; A10-B12-C22; A10-B12-C23; A10-B12-C24; A10-B12-C25;A10-B12-C26; A10-B12-C27; A10-B12-C28; A10-B12-C29; A10-B12-C30;A10-B12-C31; A10-B12-C32; A10-B12-C33; A10-B12-C34; A10-B12-C35;A10-B12-C36; A10-B12-C37; A10-B12-C38; A10-B12-C39; A10-B12-C40;A10-B12-C41; A10-B12-C42; A10-B12-C43; A10-B12-C44; A10-B12-C45;A10-B12-C46; A11-B12-C1; A11-B12-C2; A11-B12-C3; A11-B12-C4; A11-B12-C5;A11-B12-C6; A11-B12-C7; A11-B12-C8; A11-B12-C9; A11-B12-C10;A11-B12-C11; A11-B12-C12; A11-B12-C13; A11-B12-C14; A11-B12-C15;A11-B12-C16; A11-B12-C17; A11-B12-C18; A11-B12-C19; A11-B12-C20;A11-B12-C21; A11-B12-C22; A11-B12-C23; A11-B12-C24; A11-B12-C25;A11-B12-C26; A11-B12-C27; A11-B12-C28; A11-B12-C29; A11-B12-C30;A11-B12-C31; A11-B12-C32; A11-B12-C33; A11-B12-C34; A11-B12-C35;A11-B12-C36; A11-B12-C37; A11-B12-C38; A11-B12-C39; A11-B12-C40;A11-B12-C41; A11-B12-C42; A11-B12-C43; A11-B12-C44; A11-B12-C45;A11-B12-C46; A12-B12-C1; A12-B12-C2; A12-B12-C3; A12-B12-C4; A12-B12-C5;A12-B12-C6; A12-B12-C7; A12-B12-C8; A12-B12-C9; A12-B12-C10;A12-B12-C11; A12-B12-C12; A12-B12-C13; A12-B12-C14; A12-B12-C15;A12-B12-C16; A12-B12-C17; A12-B12-C18; A12-B12-C19; A12-B12-C20;A12-B12-C21; A12-B12-C22; A12-B12-C23; A12-B12-C24; A12-B12-C25;A12-B12-C26; A12-B12-C27; A12-B12-C28; A12-B12-C29; A12-B12-C30;A12-B12-C31; A12-B12-C32; A12-B12-C33; A12-B12-C34; A12-B12-C35;A12-B12-C36; A12-B12-C37; A12-B12-C38; A12-B12-C39; A12-B12-C40;A12-B12-C41; A12-B12-C42; A12-B12-C43; A12-B12-C44; A12-B12-C45;A12-B12-C46; A13-B12-C1; A13-B12-C2; A13-B12-C3; A13-B12-C4; A13-B12-C5;A13-B12-C6; A13-B12-C7; A13-B12-C8; A13-B12-C9; A13-B12-C10;A13-B12-C11; A13-B12-C12; A13-B12-C13; A13-B12-C14; A13-B12-C15;A13-B12-C16; A13-B12-C17; A13-B12-C18; A13-B12-C19; A13-B12-C20;A13-B12-C21; A13-B12-C22; A13-B12-C23; A13-B12-C24; A13-B12-C25;A13-B12-C26; A13-B12-C27; A13-B12-C28; A13-B12-C29; A13-B12-C30;A13-B12-C31; A13-B12-C32; A13-B12-C33; A13-B12-C34; A13-B12-C35;A13-B12-C36; A13-B12-C37; A13-B12-C38; A13-B12-C39; A13-B12-C40;A13-B12-C41; A13-B12-C42; A13-B12-C43; A13-B12-C44; A13-B12-C45;A13-B12-C46; A14-B12-C1; A14-B12-C2; A14-B12-C3; A14-B12-C4; A14-B12-C5;A14-B12-C6; A14-B12-C7; A14-B12-C8; A14-B12-C9; A14-B12-C10;A14-B12-C11; A14-B12-C12; A14-B12-C13; A14-B12-C14; A14-B12-C15;A14-B12-C16; A14-B12-C17; A14-B12-C18; A14-B12-C19; A14-B12-C20;A14-B12-C21; A14-B12-C22; A14-B12-C23; A14-B12-C24; A14-B12-C25;A14-B12-C26; A14-B12-C27; A14-B12-C28; A14-B12-C29; A14-B12-C30;A14-B12-C31; A14-B12-C32; A14-B12-C33; A14-B12-C34; A14-B12-C35;A14-B12-C36; A14-B12-C37; A14-B12-C38; A14-B12-C39; A14-B12-C40;A14-B12-C41; A14-B12-C42; A14-B12-C43; A14-B12-C44; A14-B12-C45;A14-B12-C46; A15-B12-C1; A15-B12-C2; A15-B12-C3; A15-B12-C4; A15-B12-C5;A15-B12-C6; A15-B12-C7; A15-B12-C8; A15-B12-C9; A15-B12-C10;A15-B12-C11; A15-B12-C12; A15-B12-C13; A15-B12-C14; A15-B12-C15;A15-B12-C16; A15-B12-C17; A15-B12-C18; A15-B12-C19; A15-B12-C20;A15-B12-C21; A15-B12-C22; A15-B12-C23; A15-B12-C24; A15-B12-C25;A15-B12-C26; A15-B12-C27; A15-B12-C28; A15-B12-C29; A15-B12-C30;A15-B12-C31; A15-B12-C32; A15-B12-C33; A15-B12-C34; A15-B12-C35;A15-B12-C36; A15-B12-C37; A15-B12-C38; A15-B12-C39; A15-B12-C40;A15-B12-C41; A15-B12-C42; A15-B12-C43; A15-B12-C44; A15-B12-C45;A15-B12-C46; A16-B12-C1; A16-B12-C2; A16-B12-C3; A16-B12-C4; A16-B12-C5;A16-B12-C6; A16-B12-C7; A16-B12-C8; A16-B12-C9; A16-B12-C10;A16-B12-C11; A16-B12-C12; A16-B12-C13; A16-B12-C14; A16-B12-C15;A16-B12-C16; A16-B12-C17; A16-B12-C18; A16-B12-C19; A16-B12-C20;A16-B12-C21; A16-B12-C22; A16-B12-C23; A16-B12-C24; A16-B12-C25;A16-B12-C26; A16-B12-C27; A16-B12-C28; A16-B12-C29; A16-B12-C30;A16-B12-C31; A16-B12-C32; A16-B12-C33; A16-B12-C34; A16-B12-C35;A16-B12-C36; A16-B12-C37; A16-B12-C38; A16-B12-C39; A16-B12-C40;A16-B12-C41; A16-B12-C42; A16-B12-C43; A16-B12-C44; A16-B12-C45;A16-B12-C46; A17-B12-C1; A17-B12-C2; A17-B12-C3; A17-B12-C4; A17-B12-C5;A17-B12-C6; A17-B12-C7; A17-B12-C8; A17-B12-C9; A17-B12-C10;A17-B12-C11; A17-B12-C12; A17-B12-C13; A17-B12-C14; A17-B12-C15;A17-B12-C16; A17-B12-C17; A17-B12-C18; A17-B12-C19; A17-B12-C20;A17-B12-C21; A17-B12-C22; A17-B12-C23; A17-B12-C24; A17-B12-C25;A17-B12-C26; A17-B12-C27; A17-B12-C28; A17-B12-C29; A17-B12-C30;A17-B12-C31; A17-B12-C32; A17-B12-C33; A17-B12-C34; A17-B12-C35;A17-B12-C36; A17-B12-C37; A17-B12-C38; A17-B12-C39; A17-B12-C40;A17-B12-C41; A17-B12-C42; A17-B12-C43; A17-B12-C44; A17-B12-C45;A17-B12-C46; A18-B12-C1; A18-B12-C2; A18-B12-C3; A18-B12-C4; A18-B12-C5;A18-B12-C6; A18-B12-C7; A18-B12-C8; A18-B12-C9; A18-B12-C10;A18-B12-C11; A18-B12-C12; A18-B12-C13; A18-B12-C14; A18-B12-C15;A18-B12-C16; A18-B12-C17; A18-B12-C18; A18-B12-C19; A18-B12-C20;A18-B12-C21; A18-B12-C22; A18-B12-C23; A18-B12-C24; A18-B12-C25;A18-B12-C26; A18-B12-C27; A18-B12-C28; A18-B12-C29; A18-B12-C30;A18-B12-C31; A18-B12-C32; A18-B12-C33; A18-B12-C34; A18-B12-C35;A18-B12-C36; A18-B12-C37; A18-B12-C38; A18-B12-C39; A18-B12-C40;A18-B12-C41; A18-B12-C42; A18-B12-C43; A18-B12-C44; A18-B12-C45;A18-B12-C46; A19-B12-C1; A19-B12-C2; A19-B12-C3; A19-B12-C4; A19-B12-C5;A19-B12-C6; A19-B12-C7; A19-B12-C8; A19-B12-C9; A19-B12-C10;A19-B12-C11; A19-B12-C12; A19-B12-C13; A19-B12-C14; A19-B12-C15;A19-B12-C16; A19-B12-C17; A19-B12-C18; A19-B12-C19; A19-B12-C20;A19-B12-C21; A19-B12-C22; A19-B12-C23; A19-B12-C24; A19-B12-C25;A19-B12-C26; A19-B12-C27; A19-B12-C28; A19-B12-C29; A19-B12-C30;A19-B12-C31; A19-B12-C32; A19-B12-C33; A19-B12-C34; A19-B12-C35;A19-B12-C36; A19-B12-C37; A19-B12-C38; A19-B12-C39; A19-B12-C40;A19-B12-C41; A19-B12-C42; A19-B12-C43; A19-B12-C44; A19-B12-C45;A19-B12-C46; A20-B12-C1; A20-B12-C2; A20-B12-C3; A20-B12-C4; A20-B12-C5;A20-B12-C6; A20-B12-C7; A20-B12-C8; A20-B12-C9; A20-B12-C10;A20-B12-C11; A20-B12-C12; A20-B12-C13; A20-B12-C14; A20-B12-C15;A20-B12-C16; A20-B12-C17; A20-B12-C18; A20-B12-C19; A20-B12-C20;A20-B12-C21; A20-B12-C22; A20-B12-C23; A20-B12-C24; A20-B12-C25;A20-B12-C26; A20-B12-C27; A20-B12-C28; A20-B12-C29; A20-B12-C30;A20-B12-C31; A20-B12-C32; A20-B12-C33; A20-B12-C34; A20-B12-C35;A20-B12-C36; A20-B12-C37; A20-B12-C38; A20-B12-C39; A20-B12-C40;A20-B12-C41; A20-B12-C42; A20-B12-C43; A20-B12-C44; A20-B12-C45;A20-B12-C46; A21-B12-C1; A21-B12-C2; A21-B12-C3; A21-B12-C4; A21-B12-C5;A21-B12-C6; A21-B12-C7; A21-B12-C8; A21-B12-C9; A21-B12-C10;A21-B12-C11; A21-B12-C12; A21-B12-C13; A21-B12-C14; A21-B12-C15;A21-B12-C16; A21-B12-C17; A21-B12-C18; A21-B12-C19; A21-B12-C20;A21-B12-C21; A21-B12-C22; A21-B12-C23; A21-B12-C24; A21-B12-C25;A21-B12-C26; A21-B12-C27; A21-B12-C28; A21-B12-C29; A21-B12-C30;A21-B12-C31; A21-B12-C32; A21-B12-C33; A21-B12-C34; A21-B12-C35;A21-B12-C36; A21-B12-C37; A21-B12-C38; A21-B12-C39; A21-B12-C40;A21-B12-C41; A21-B12-C42; A21-B12-C43; A21-B12-C44; A21-B12-C45;A21-B12-C46; A22-B12-C1; A22-B12-C2; A22-B12-C3; A22-B12-C4; A22-B12-C5;A22-B12-C6; A22-B12-C7; A22-B12-C8; A22-B12-C9; A22-B12-C10;A22-B12-C11; A22-B12-C12; A22-B12-C13; A22-B12-C14; A22-B12-C15;A22-B12-C16; A22-B12-C17; A22-B12-C18; A22-B12-C19; A22-B12-C20;A22-B12-C21; A22-B12-C22; A22-B12-C23; A22-B12-C24; A22-B12-C25;A22-B12-C26; A22-B12-C27; A22-B12-C28; A22-B12-C29; A22-B12-C30;A22-B12-C31; A22-B12-C32; A22-B12-C33; A22-B12-C34; A22-B12-C35;A22-B12-C36; A22-B12-C37; A22-B12-C38; A22-B12-C39; A22-B12-C40;A22-B12-C41; A22-B12-C42; A22-B12-C43; A22-B12-C44; A22-B12-C45;A22-B12-C46; A23-B12-C1; A23-B12-C2; A23-B12-C3; A23-B12-C4; A23-B12-C5;A23-B12-C6; A23-B12-C7; A23-B12-C8; A23-B12-C9; A23-B12-C10;A23-B12-C11; A23-B12-C12; A23-B12-C13; A23-B12-C14; A23-B12-C15;A23-B12-C16; A23-B12-C17; A23-B12-C18; A23-B12-C19; A23-B12-C20;A23-B12-C21; A23-B12-C22; A23-B12-C23; A23-B12-C24; A23-B12-C25;A23-B12-C26; A23-B12-C27; A23-B12-C28; A23-B12-C29; A23-B12-C30;A23-B12-C31; A23-B12-C32; A23-B12-C33; A23-B12-C34; A23-B12-C35;A23-B12-C36; A23-B12-C37; A23-B12-C38; A23-B12-C39; A23-B12-C40;A23-B12-C41; A23-B12-C42; A23-B12-C43; A23-B12-C44; A23-B12-C45;A23-B12-C46; A24-B12-C1; A24-B12-C2; A24-B12-C3; A24-B12-C4; A24-B12-C5;A24-B12-C6; A24-B12-C7; A24-B12-C8; A24-B12-C9; A24-B12-C10;A24-B12-C11; A24-B12-C12; A24-B12-C13; A24-B12-C14; A24-B12-C15;A24-B12-C16; A24-B12-C17; A24-B12-C18; A24-B12-C19; A24-B12-C20;A24-B12-C21; A24-B12-C22; A24-B12-C23; A24-B12-C24; A24-B12-C25;A24-B12-C26; A24-B12-C27; A24-B12-C28; A24-B12-C29; A24-B12-C30;A24-B12-C31; A24-B12-C32; A24-B12-C33; A24-B12-C34; A24-B12-C35;A24-B12-C36; A24-B12-C37; A24-B12-C38; A24-B12-C39; A24-B12-C40;A24-B12-C41; A24-B12-C42; A24-B12-C43; A24-B12-C44; A24-B12-C45;A24-B12-C46; A25-B12-C1; A25-B12-C2; A25-B12-C3; A25-B12-C4; A25-B12-C5;A25-B12-C6; A25-B12-C7; A25-B12-C8; A25-B12-C9: A25-B12-C10:A25-B12-C11; A25-B12-C12; A25-B12-C13; A25-B12-C14; A25-B12-C15;A25-B12-C16; A25-B12-C17; A25-B12-C18; A25-B12-C19; A25-B12-C20;A25-B12-C21; A25-B12-C22; A25-B12-C23; A25-B12-C24; A25-B12-C25;A25-B12-C26; A25-B12-C27; A25-B12-C28; A25-B12-C29; A25-B12-C30;A25-B12-C31; A25-B12-C32; A25-B12-C33; A25-B12-C34; A25-B12-C35;A25-B12-C36; A25-B12-C37; A25-B12-C38; A25-B12-C39; A25-B12-C40;A25-B12-C41; A25-B12-C42; A25-B12-C43; A25-B12-C44; A25-B12-C45;A25-B12-C46; A26-B12-C1; A26-B12-C2; A26-B12-C3; A26-B12-C4; A26-B12-C5;A26-B12-C6; A26-B12-C7; A26-B12-C8; A26-B12-C9; A26-B12-C10;A26-B12-C11; A26-B12-C12; A26-B12-C13; A26-B12-C14; A26-B12-C15;A26-B12-C16; A26-B12-C17; A26-B12-C18; A26-B12-C19; A26-B12-C20;A26-B12-C21; A26-B12-C22; A26-B12-C23; A26-B12-C24; A26-B12-C25;A26-B12-C26; A26-B12-C27; A26-B12-C28; A26-B12-C29; A26-B12-C30;A26-B12-C31; A26-B12-C32; A26-B12-C33; A26-B12-C34; A26-B12-C35;A26-B12-C36; A26-B12-C37; A26-B12-C38; A26-B12-C39; A26-B12-C40;A26-B12-C41; A26-B12-C42; A26-B12-C43; A26-B12-C44; A26-B12-C45;A26-B12-C46; A27-B12-C1; A27-B12-C2; A27-B12-C3; A27-B12-C4; A27-B12-C5;A27-B12-C6; A27-B12-C7; A27-B12-C8; A27-B12-C9; A27-B12-C10;A27-B12-C11; A27-B12-C12; A27-B12-C13; A27-B12-C14; A27-B12-C15;A27-B12-C16; A27-B12-C17; A27-B12-C18; A27-B12-C19; A27-B12-C20;A27-B12-C21; A27-B12-C22; A27-B12-C23; A27-B12-C24; A27-B12-C25;A27-B12-C26; A27-B12-C27; A27-B12-C28; A27-B12-C29; A27-B12-C30;A27-B12-C31; A27-B12-C32; A27-B12-C33; A27-B12-C34; A27-B12-C35;A27-B12-C36; A27-B12-C37; A27-B12-C38; A27-B12-C39; 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A1-B13-C31; A1-B13-C32; A1-B13-C33; A1-B13-C34; A1-B13-C35;A1-B13-C36; A1-B13-C37; A1-B13-C38; A1-B13-C39; A1-B13-C40; A1-B13-C41;A1-B13-C42; A1-B13-C43; A1-B13-C44; A1-B13-C45; A1-B13-C46; A2-B13-C1;A2-B13-C2; A2-B13-C3; A2-B13-C4; A2-B13-C5; A2-B13-C6; A2-B13-C7;A2-B13-C8; A2-B13-C9; A2-B13-C10; A2-B13-C11; A2-B13-C12; A2-B13-C13;A2-B13-C14; A2-B13-C15; A2-B13-C16; A2-B13-C17; A2-B13-C18; A2-B13-C19;A2-B13-C20; A2-B13-C21; A2-B13-C22; A2-B13-C23; A2-B13-C24; A2-B13-C25;A2-B13-C26; A2-B13-C27; A2-B13-C28; A2-B13-C29; A2-B13-C30; A2-B13-C31;A2-B13-C32; A2-B13-C33; A2-B13-C34; A2-B13-C35; A2-B13-C36; A2-B13-C37;A2-B13-C38; A2-B13-C39; A2-B13-C40; A2-B13-C41; A2-B13-C42; A2-B13-C43;A2-B13-C44; A2-B13-C45; A2-B13-C46; A3-B13-C1; A3-B13-C2; A3-B13-C3;A3-B13-C4; A3-B13-C5; A3-B13-C6; A3-B13-C7; A3-B13-C8; A3-B13-C9;A3-B13-C10; A3-B13-C11; A3-B13-C12; A3-B13-C13; A3-B13-C14; A3-B13-C15;A3-B13-C16; A3-B13-C17; A3-B13-C18; A3-B13-C19; A3-B13-C20; A3-B13-C21;A3-B13-C22; A3-B13-C23; A3-B13-C24; A3-B13-C25; A3-B13-C26; A3-B13-C27;A3-B13-C28; A3-B13-C29; A3-B13-C30; A3-B13-C31; A3-B13-C32; A3-B13-C33;A3-B13-C34; A3-B13-C35; A3-B13-C36; A3-B13-C37; A3-B13-C38; A3-B13-C39;A3-B13-C40; A3-B13-C41; A3-B13-C42; A3-B13-C43; A3-B13-C44; A3-B13-C45;A3-B13-C46; A4-B13-C1; A4-B13-C2; A4-B13-C3; A4-B13-C4; A4-B13-C5;A4-B13-C6; A4-B13-C7; A4-B13-C8; A4-B13-C9; A4-B13-C10; A4-B13-C11;A4-B13-C12; A4-B13-C13; A4-B13-C14; A4-B13-C15; A4-B13-C16; A4-B13-C17;A4-B13-C18; A4-B13-C19; A4-B13-C20; A4-B13-C21; A4-B13-C22; A4-B13-C23;A4-B13-C24; A4-B13-C25; A4-B13-C26; A4-B13-C27; A4-B13-C28; A4-B13-C29;A4-B13-C30; A4-B13-C31; A4-B13-C32; A4-B13-C33; A4-B13-C34; A4-B13-C35;A4-B13-C36; A4-B13-C37; A4-B13-C38; A4-B13-C39; A4-B13-C40; A4-B13-C41;A4-B13-C42; A4-B13-C43; A4-B13-C44; A4-B13-C45; A4-B13-C46; A5-B13-C1;A5-B13-C2; A5-B13-C3; A5-B13-C4; A5-B13-C5; A5-B13-C6; A5-B13-C7;A5-B13-C8; A5-B13-C9; A5-B13-C10; A5-B13-C11; A5-B13-C12; A5-B13-C13;A5-B13-C14; A5-B13-C15; A5-B13-C16; A5-B13-C17; A5-B13-C18; A5-B13-C19;A5-B13-C20; A5-B13-C21; A5-B13-C22; A5-B13-C23; A5-B13-C24; A5-B13-C25;A5-B13-C26; A5-B13-C27; A5-B13-C28; A5-B13-C29; A5-B13-C30; A5-B13-C31;A5-B13-C32; A5-B13-C33; A5-B13-C34; A5-B13-C35; A5-B13-C36; A5-B13-C37;A5-B13-C38; A5-B13-C39; A5-B13-C40; A5-B13-C41; A5-B13-C42; A5-B13-C43;A5-B13-C44; A5-B13-C45; A5-B13-C46; A6-B13-C1; A6-B13-C2; A6-B13-C3;A6-B13-C4; A6-B13-C5; A6-B13-C6; A6-B13-C7; A6-B13-C8; A6-B13-C9;A6-B13-C10; A6-B13-C11; A6-B13-C12; A6-B13-C13; A6-B13-C14; A6-B13-C15;A6-B13-C16; A6-B13-C17; A6-B13-C18; A6-B13-C19; A6-B13-C20; A6-B13-C21;A6-B13-C22; A6-B13-C23; A6-B13-C24; A6-B13-C25; A6-B13-C26; A6-B13-C27;A6-B13-C28; A6-B13-C29; A6-B13-C30; A6-B13-C31; A6-B13-C32; A6-B13-C33;A6-B13-C34; A6-B13-C35; A6-B13-C36; A6-B13-C37; A6-B13-C38; A6-B13-C39;A6-B13-C40; A6-B13-C41; A6-B13-C42; A6-B13-C43; A6-B13-C44; A6-B13-C45;A6-B13-C46; A7-B13-C1; A7-B13-C2; A7-B13-C3; A7-B13-C4; A7-B13-C5;A7-B13-C6; A7-B13-C7; A7-B13-C8; A7-B13-C9; A7-B13-C10; A7-B13-C11;A7-B13-C12; A7-B13-C13; A7-B13-C14; A7-B13-C15; A7-B13-C16; A7-B13-C17;A7-B13-C18; A7-B13-C19; A7-B13-C20; A7-B13-C21; A7-B13-C22; A7-B13-C23;A7-B13-C24; A7-B13-C25; A7-B13-C26; A7-B13-C27; A7-B13-C28; A7-B13-C29;A7-B13-C30; A7-B13-C31; A7-B13-C32; A7-B13-C33; A7-B13-C34; A7-B13-C35;A7-B13-C36; A7-B13-C37; A7-B13-C38; A7-B13-C39; A7-B13-C40; A7-B13-C41;A7-B13-C42; A7-B13-C43; A7-B13-C44; A7-B13-C45; A7-B13-C46; A8-B13-C1;A8-B13-C2; A8-B13-C3; A8-B13-C4; A8-B13-C5; A8-B13-C6; A8-B13-C7;A8-B13-C8; A8-B13-C9; A8-B13-C10; A8-B13-C11; A8-B13-C12; A8-B13-C13;A8-B13-C14; A8-B13-C15; A8-B13-C16; A8-B13-C17; A8-B13-C18; A8-B13-C19;A8-B13-C20; A8-B13-C21; A8-B13-C22; A8-B13-C23; A8-B13-C24; A8-B13-C25;A8-B13-C26; A8-B13-C27; A8-B13-C28; A8-B13-C29; A8-B13-C30; A8-B13-C31;A8-B13-C32; A8-B13-C33; A8-B13-C34; A8-B13-C35; A8-B13-C36; A8-B13-C37;A8-B13-C38; A8-B13-C39; A8-B13-C40; A8-B13-C41; A8-B13-C42; A8-B13-C43;A8-B13-C44; A8-B13-C45; A8-B13-C46; A9-B13-C1; A9-B13-C2; A9-B13-C3;A9-B13-C4; A9-B13-C5; A9-B13-C6; A9-B13-C7; A9-B13-C8; A9-B13-C9;A9-B13-C10; A9-B13-C11; A9-B13-C12; A9-B13-C13; A9-B13-C14; A9-B13-C15;A9-B13-C16; A9-B13-C17; A9-B13-C18; A9-B13-C19; A9-B13-C20; A9-B13-C21;A9-B13-C22; A9-B13-C23; A9-B13-C24; A9-B13-C25; A9-B13-C26; A9-B13-C27;A9-B13-C28; A9-B13-C29; A9-B13-C30; A9-B13-C31; A9-B13-C32; A9-B13-C33;A9-B13-C34; A9-B13-C35; A9-B13-C36; A9-B13-C37; A9-B13-C38; A9-B13-C39;A9-B13-C40; A9-B13-C41; A9-B13-C42; A9-B13-C43; A9-B13-C44; A9-B13-C45;A9-B13-C46; A10-B13-C1; A10-B13-C2; A10-B13-C3; A10-B13-C4; A10-B13-C5;A10-B13-C6; A10-B13-C7; A10-B13-C8; A10-B13-C9; A10-B13-C10;A10-B13-C11; A10-B13-C12; A10-B13-C13; A10-B13-C14; A10-B13-C15;A10-B13-C16; A10-B13-C17; A10-B13-C18; A10-B13-C19; A10-B13-C20;A10-B13-C21; A10-B13-C22; A10-B13-C23; A10-B13-C24; A10-B13-C25;A10-B13-C26; A10-B13-C27; A10-B13-C28; A10-B13-C29; A10-B13-C30;A10-B13-C31; A10-B13-C32; A10-B13-C33; A10-B13-C34; A10-B13-C35;A10-B13-C36; A10-B13-C37; A10-B13-C38; A10-B13-C39; A10-B13-C40;A10-B13-C41; A10-B13-C42; A10-B13-C43; A10-B13-C44; A10-B13-C45;A10-B13-C46; A11-B13-C1; A11-B13-C2; A11-B13-C3; A11-B13-C4; A11-B13-C5;A11-B13-C6; A11-B13-C7; A11-B13-C8; A11-B13-C9; A11-B13-C10;A11-B13-C11; A11-B13-C12; A11-B13-C13; A11-B13-C14; A11-B13-C15;A11-B13-C16; A11-B13-C17; A11-B13-C18; A11-B13-C19; A11-B13-C20;A11-B13-C21; A11-B13-C22; A11-B13-C23; A11-B13-C24; A11-B13-C25;A11-B13-C26; A11-B13-C27; A11-B13-C28; A11-B13-C29; A11-B13-C30;A11-B13-C31; A11-B13-C32; A11-B13-C33; A11-B13-C34; A11-B13-C35;A11-B13-C36; A11-B13-C37; A11-B13-C38; A11-B13-C39; A11-B13-C40;A11-B13-C41; A11-B13-C42; A11-B13-C43; A11-B13-C44; A11-B13-C45;A11-B13-C46; A12-B13-C1; A12-B13-C2; A12-B13-C3; A12-B13-C4; A12-B13-C5;A12-B13-C6; A12-B13-C7; A12-B13-C8; A12-B13-C9; A12-B13-C10;A12-B13-C11; A12-B13-C12; A12-B13-C13; A12-B13-C14; A12-B13-C15;A12-B13-C16; A12-B13-C17; A12-B13-C18; A12-B13-C19; A12-B13-C20;A12-B13-C21; A12-B13-C22; A12-B13-C23; A12-B13-C24; A12-B13-C25;A12-B13-C26; A12-B13-C27; A12-B13-C28; A12-B13-C29; A12-B13-C30;A12-B13-C31; A12-B13-C32; A12-B13-C33; A12-B13-C34; A12-B13-C35;A12-B13-C36; A12-B13-C37; A12-B13-C38; A12-B13-C39; A12-B13-C40;A12-B13-C41; A12-B13-C42; A12-B13-C43; A12-B13-C44; A12-B13-C45;A12-B13-C46; A13-B13-C1; A13-B13-C2; A13-B13-C3; A13-B13-C4; A13-B13-C5;A13-B13-C6; A13-B13-C7; A13-B13-C8; A13-B13-C9; A13-B13-C10;A13-B13-C11; A13-B13-C12; A13-B13-C13; A13-B13-C14; A13-B13-C15;A13-B13-C16; A13-B13-C17; A13-B13-C18; A13-B13-C19; A13-B13-C20;A13-B13-C21; A13-B13-C22; A13-B13-C23; A13-B13-C24; A13-B13-C25;A13-B13-C26; A13-B13-C27; A13-B13-C28; A13-B13-C29; A13-B13-C30;A13-B13-C31; A13-B13-C32; A13-B13-C33; A13-B13-C34; A13-B13-C35;A13-B13-C36; A13-B13-C37; A13-B13-C38; A13-B13-C39; A13-B13-C40;A13-B13-C41; A13-B13-C42; A13-B13-C43; A13-B13-C44; A13-B13-C45;A13-B13-C46; A14-B13-C1; A14-B13-C2; A14-B13-C3; A14-B13-C4; A14-B13-C5;A14-B13-C6; A14-B13-C7; A14-B13-C8; A14-B13-C9; A14-B13-C10;A14-B13-C11; A14-B13-C12; A14-B13-C13; A14-B13-C14; A14-B13-C15;A14-B13-C16; A14-B13-C17; A14-B13-C18; A14-B13-C19; A14-B13-C20;A14-B13-C21; A14-B13-C22; A14-B13-C23; A14-B13-C24; A14-B13-C25;A14-B13-C26; A14-B13-C27; A14-B13-C28; A14-B13-C29; A14-B13-C30;A14-B13-C31; A14-B13-C32; A14-B13-C33; A14-B13-C34; A14-B13-C35;A14-B13-C36; A14-B13-C37; A14-B13-C38; A14-B13-C39; A14-B13-C40;A14-B13-C41; A14-B13-C42; A14-B13-C43; A14-B13-C44; A14-B13-C45;A14-B13-C46; A15-B13-C1; A15-B13-C2; A15-B13-C3; A15-B13-C4; A15-B13-C5;A15-B13-C6; A15-B13-C7; A15-B13-C8; A15-B13-C9; A15-B13-C10;A15-B13-C11; A15-B13-C12; A15-B13-C13; A15-B13-C14; A15-B13-C15;A15-B13-C16; A15-B13-C17; A15-B13-C18; A15-B13-C19; A15-B13-C20;A15-B13-C21; A15-B13-C22; A15-B13-C23; A15-B13-C24; A15-B13-C25;A15-B13-C26; A15-B13-C27; A15-B13-C28; A15-B13-C29; A15-B13-C30;A15-B13-C31; A15-B13-C32; A15-B13-C33; A15-B13-C34; A15-B13-C35;A15-B13-C36; A15-B13-C37; A15-B13-C38; A15-B13-C39; A15-B13-C40;A15-B13-C41; A15-B13-C42; A15-B13-C43; A15-B13-C44; A15-B13-C45;A15-B13-C46; A16-B13-C1; A16-B13-C2; A16-B13-C3; A16-B13-C4; A16-B13-C5;A16-B13-C6; A16-B13-C7; A16-B13-C8; A16-B13-C9; A16-B13-C10;A16-B13-C11; A16-B13-C12; A16-B13-C13; A16-B13-C14; A16-B13-C15;A16-B13-C16; A16-B13-C17; A16-B13-C18; A16-B13-C19; A16-B13-C20;A16-B13-C21; A16-B13-C22; A16-B13-C23; A16-B13-C24; A16-B13-C25;A16-B13-C26; A16-B13-C27; A16-B13-C28; A16-B13-C29; A16-B13-C30;A16-B13-C31; A16-B13-C32; A16-B13-C33; A16-B13-C34; A16-B13-C35;A16-B13-C36; A16-B13-C37; A16-B13-C38; A16-B13-C39; A16-B13-C40;A16-B13-C41; A16-B13-C42; A16-B13-C43; A16-B13-C44; A16-B13-C45;A16-B13-C46; A17-B13-C1; A17-B13-C2; A17-B13-C3; A17-B13-C4; A17-B13-C5;A17-B13-C6; A17-B13-C7; A17-B13-C8; A17-B13-C9; A17-B13-C10;A17-B13-C11; A17-B13-C12; A17-B13-C13; A17-B13-C14; A17-B13-C15;A17-B13-C16; A17-B13-C17; A17-B13-C18; A17-B13-C19; A17-B13-C20;A17-B13-C21; A17-B13-C22; A17-B13-C23; A17-B13-C24; A17-B13-C25;A17-B13-C26; A17-B13-C27; A17-B13-C28; A17-B13-C29; A17-B13-C30;A17-B13-C31; A17-B13-C32; A17-B13-C33; A17-B13-C34; A17-B13-C35;A17-B13-C36; A17-B13-C37; A17-B13-C38; A17-B13-C39; A17-B13-C40;A17-B13-C41; A17-B13-C42; A17-B13-C43; A17-B13-C44; A17-B13-C45;A17-B13-C46; A18-B13-C1; A18-B13-C2; A18-B13-C3; A18-B13-C4; A18-B13-C5;A18-B13-C6; A18-B13-C7; A18-B13-C8; A18-B13-C9; A18-B13-C10;A18-B13-C11; A18-B13-C12; A18-B13-C13; A18-B13-C14; A18-B13-C15;A18-B13-C16; A18-B13-C17; A18-B13-C18; A18-B13-C19; A18-B13-C20;A18-B13-C21; A18-B13-C22; A18-B13-C23; A18-B13-C24; A18-B13-C25;A18-B13-C26; A18-B13-C27; A18-B13-C28; A18-B13-C29; A18-B13-C30;A18-B13-C31; A18-B13-C32; A18-B13-C33; A18-B13-C34; A18-B13-C35;A18-B13-C36; A18-B13-C37; A18-B13-C38; A18-B13-C39; A18-B13-C40;A18-B13-C41; A18-B13-C42; A18-B13-C43; A18-B13-C44; A18-B13-C45;A18-B13-C46; A19-B13-C1; A19-B13-C2; A19-B13-C3; A19-B13-C4; A19-B13-C5;A19-B13-C6; A19-B13-C7; A19-B13-C8; A19-B13-C9; A19-B13-C10;A19-B13-C11; A19-B13-C12; A19-B13-C13; A19-B13-C14; A19-B13-C15;A19-B13-C16; A19-B13-C17; A19-B13-C18; A19-B13-C19; A19-B13-C20;A19-B13-C21; A19-B13-C22; A19-B13-C23; A19-B13-C24; A19-B13-C25;A19-B13-C26; A19-B13-C27; A19-B13-C28; A19-B13-C29; A19-B13-C30;A19-B13-C31; A19-B13-C32; A19-B13-C33; A19-B13-C34; A19-B13-C35;A19-B13-C36; A19-B13-C37; A19-B13-C38; A19-B13-C39; A19-B13-C40;A19-B13-C41; A19-B13-C42; A19-B13-C43; A19-B13-C44; A19-B13-C45;A19-B13-C46; A20-B13-C1; A20-B13-C2; A20-B13-C3; A20-B13-C4; A20-B13-C5;A20-B13-C6; A20-B13-C7; A20-B13-C8; A20-B13-C9; A20-B13-C10;A20-B13-C11; A20-B13-C12; A20-B13-C13; A20-B13-C14; A20-B13-C15;A20-B13-C16; A20-B13-C17; A20-B13-C18; A20-B13-C19; A20-B13-C20;A20-B13-C21; A20-B13-C22; A20-B13-C23; A20-B13-C24; A20-B13-C25;A20-B13-C26; A20-B13-C27; A20-B13-C28; A20-B13-C29; A20-B13-C30;A20-B13-C31; A20-B13-C32; A20-B13-C33; A20-B13-C34; A20-B13-C35;A20-B13-C36; A20-B13-C37; A20-B13-C38; A20-B13-C39; A20-B13-C40;A20-B13-C41; A20-B13-C42; A20-B13-C43; A20-B13-C44; A20-B13-C45;A20-B13-C46; A21-B13-C1; A21-B13-C2; A21-B13-C3; A21-B13-C4; A21-B13-C5;A21-B13-C6; A21-B13-C7; A21-B13-C8; A21-B13-C9; A21-B13-C10;A21-B13-C11; A21-B13-C12; A21-B13-C13; A21-B13-C14; A21-B13-C15;A21-B13-C16; A21-B13-C17; A21-B13-C18; A21-B13-C19; A21-B13-C20;A21-B13-C21; A21-B13-C22; A21-B13-C23; A21-B13-C24; A21-B13-C25;A21-B13-C26; A21-B13-C27; A21-B13-C28; A21-B13-C29; A21-B13-C30;A21-B13-C31; A21-B13-C32; A21-B13-C33; A21-B13-C34; A21-B13-C35;A21-B13-C36; A21-B13-C37; A21-B13-C38; A21-B13-C39; A21-B13-C40;A21-B13-C41; A21-B13-C42; A21-B13-C43; A21-B13-C44; A21-B13-C45;A21-B13-C46; A22-B13-C1; A22-B13-C2; A22-B13-C3; A22-B13-C4; A22-B13-C5;A22-B13-C6; A22-B13-C7; A22-B13-C8; A22-B13-C9; A22-B13-C10;A22-B13-C11; A22-B13-C12; A22-B13-C13; A22-B13-C14; A22-B13-C15;A22-B13-C16; A22-B13-C17; A22-B13-C18; A22-B13-C19; A22-B13-C20;A22-B13-C21; A22-B13-C22; A22-B13-C23; A22-B13-C24; A22-B13-C25;A22-B13-C26; A22-B13-C27; A22-B13-C28; A22-B13-C29; A22-B13-C30;A22-B13-C31; A22-B13-C32; A22-B13-C33; A22-B13-C34; A22-B13-C35;A22-B13-C36; A22-B13-C37; A22-B13-C38; A22-B13-C39; A22-B13-C40;A22-B13-C41; A22-B13-C42; A22-B13-C43; A22-B13-C44; A22-B13-C45;A22-B13-C46; A23-B13-C1; A23-B13-C2; A23-B13-C3; A23-B13-C4; A23-B13-C5;A23-B13-C6; A23-B13-C7; A23-B13-C8; A23-B13-C9; A23-B13-C10;A23-B13-C11; A23-B13-C12; A23-B13-C13; A23-B13-C14; A23-B13-C15;A23-B13-C16; A23-B13-C17; A23-B13-C18; A23-B13-C19; A23-B13-C20;A23-B13-C21; A23-B13-C22; A23-B13-C23; A23-B13-C24; A23-B13-C25;A23-B13-C26; A23-B13-C27; A23-B13-C28; A23-B13-C29; A23-B13-C30;A23-B13-C31; A23-B13-C32; A23-B13-C33; A23-B13-C34; A23-B13-C35;A23-B13-C36; A23-B13-C37; A23-B13-C38; A23-B13-C39; A23-B13-C40;A23-B13-C41; A23-B13-C42; A23-B13-C43; A23-B13-C44; A23-B13-C45;A23-B13-C46; A24-B13-C1; A24-B13-C2; A24-B13-C3; A24-B13-C4; A24-B13-C5;A24-B13-C6; A24-B13-C7; A24-B13-C8; A24-B13-C9; A24-B13-C10;A24-B13-C11; A24-B13-C12; A24-B13-C13; A24-B13-C14; A24-B13-C15;A24-B13-C16; A24-B13-C17; A24-B13-C18; A24-B13-C19; A24-B13-C20;A24-B13-C21; A24-B13-C22; A24-B13-C23; A24-B13-C24; A24-B13-C25;A24-B13-C26; A24-B13-C27; A24-B13-C28; A24-B13-C29; A24-B13-C30;A24-B13-C31; A24-B13-C32; A24-B13-C33; A24-B13-C34; A24-B13-C35;A24-B13-C36; A24-B13-C37; A24-B13-C38; A24-B13-C39; A24-B13-C40;A24-B13-C41; A24-B13-C42; A24-B13-C43; A24-B13-C44; A24-B13-C45;A24-B13-C46; A25-B13-C1; A25-B13-C2; A25-B13-C3; A25-B13-C4; A25-B13-C5;A25-B13-C6; A25-B13-C7; A25-B13-C8; A25-B13-C9; A25-B13-C10;A25-B13-C11; A25-B13-C12; A25-B13-C13; A25-B13-C14; A25-B13-C15;A25-B13-C16; A25-B13-C17; A25-B13-C18; A25-B13-C19; A25-B13-C20;A25-B13-C21; A25-B13-C22; A25-B13-C23; A25-B13-C24; A25-B13-C25;A25-B13-C26; A25-B13-C27; A25-B13-C28; A25-B13-C29; A25-B13-C30;A25-B13-C31; A25-B13-C32; A25-B13-C33; A25-B13-C34; A25-B13-C35;A25-B13-C36; A25-B13-C37; A25-B13-C38; A25-B13-C39; A25-B13-C40;A25-B13-C41; A25-B13-C42; A25-B13-C43; A25-B13-C44; A25-B13-C45;A25-B13-C46; A26-B13-C1; A26-B13-C2; A26-B13-C3; A26-B13-C4; A26-B13-C5;A26-B13-C6; A26-B13-C7; A26-B13-C8; A26-B13-C9; A26-B13-C10;A26-B13-C11; A26-B13-C12; A26-B13-C13; A26-B13-C14; A26-B13-C15;A26-B13-C16; A26-B13-C17; A26-B13-C18; A26-B13-C19; A26-B13-C20;A26-B13-C21; A26-B13-C22; A26-B13-C23; A26-B13-C24; A26-B13-C25;A26-B13-C26; A26-B13-C27; A26-B13-C28; A26-B13-C29; A26-B13-C30;A26-B13-C31; A26-B13-C32; A26-B13-C33; A26-B13-C34; A26-B13-C35;A26-B13-C36; A26-B13-C37; A26-B13-C38; A26-B13-C39; A26-B13-C40;A26-B13-C41; A26-B13-C42; A26-B13-C43; A26-B13-C44; A26-B13-C45;A26-B13-C46; A27-B13-C1; A27-B13-C2; A27-B13-C3; A27-B13-C4; A27-B13-C5;A27-B13-C6; A27-B13-C7; A27-B13-C8; A27-B13-C9; A27-B13-C10;A27-B13-C11; A27-B13-C12; A27-B13-C13; A27-B13-C14; A27-B13-C15;A27-B13-C16; A27-B13-C17; A27-B13-C18; A27-B13-C19; A27-B13-C20;A27-B13-C21; A27-B13-C22; A27-B13-C23; A27-B13-C24; A27-B13-C25;A27-B13-C26; A27-B13-C27; A27-B13-C28; A27-B13-C29; A27-B13-C30;A27-B13-C31; A27-B13-C32; A27-B13-C33; A27-B13-C34; A27-B13-C35;A27-B13-C36; A27-B13-C37; A27-B13-C38; A27-B13-C39; A27-B13-C40;A27-B13-C41; A27-B13-C42; A27-B13-C43; A27-B13-C44; A27-B13-C45;A27-B13-C46; A28-B13-C1; A28-B13-C2; A28-B13-C3; A28-B13-C4; A28-B13-C5;A28-B13-C6; A28-B13-C7; A28-B13-C8; A28-B13-C9; A28-B13-C10;A28-B13-C11; A28-B13-C12; A28-B13-C13; A28-B13-C14; A28-B13-C15;A28-B13-C16; A28-B13-C17; A28-B13-C18; A28-B13-C19; A28-B13-C20;A28-B13-C21; A28-B13-C22; A28-B13-C23; A28-B13-C24; A28-B13-C25;A28-B13-C26; A28-B13-C27; A28-B13-C28; A28-B13-C29; A28-B13-C30;A28-B13-C31; A28-B13-C32; A28-B13-C33; A28-B13-C34; A28-B13-C35;A28-B13-C36; A28-B13-C37; A28-B13-C38; A28-B13-C39; A28-B13-C40;A28-B13-C41; A28-B13-C42; A28-B13-C43; A28-B13-C44; A28-B13-C45;A28-B13-C46; A1-B14-C1; A1-B14-C2; A1-B14-C3; A1-B14-C4; A1-B14-C5;A1-B14-C6; A1-B14-C7; A1-B14-C8; A1-B14-C9; A1-B14-C10; A1-B14-C11;A1-B14-C12; A1-B14-C13; A1-B14-C14; A1-B14-C15; A1-B14-C16; A1-B14-C17;A1-B14-C18; A1-B14-C19; A1-B14-C20; A1-B14-C21; A1-B14-C22; A1-B14-C23;A1-B14-C24; A1-B14-C25; A1-B14-C26; A1-B14-C27; A1-B14-C28; A1-B14-C29;A1-B14-C30; A1-B14-C31; A1-B14-C32; A1-B14-C33; A1-B14-C34; A1-B14-C35;A1-B14-C36; A1-B14-C37; A1-B14-C38; A1-B14-C39; A1-B14-C40; A1-B14-C41;A1-B14-C42; A1-B14-C43; A1-B14-C44; A1-B14-C45; A1-B14-C46; A2-B14-C1;A2-B14-C2; A2-B14-C3; A2-B14-C4; A2-B14-C5; A2-B14-C6; A2-B14-C7;A2-B14-C8; A2-B14-C9; A2-B14-C10; A2-B14-C11; A2-B14-C12; A2-B14-C13;A2-B14-C14; A2-B14-C15; A2-B14-C16; A2-B14-C17; A2-B14-C18; A2-B14-C19;A2-B14-C20; A2-B14-C21; A2-B14-C22; A2-B14-C23; A2-B14-C24; A2-B14-C25;A2-B14-C26; A2-B14-C27; A2-B14-C28; A2-B14-C29; A2-B14-C30; A2-B14-C31;A2-B14-C32; A2-B14-C33; A2-B14-C34; A2-B14-C35; A2-B14-C36; A2-B14-C37;A2-B14-C38; A2-B14-C39; A2-B14-C40; A2-B14-C41; A2-B14-C42; A2-B14-C43;A2-B14-C44; A2-B14-C45; A2-B14-C46; A3-B14-C1; A3-B14-C2; A3-B14-C3;A3-B14-C4; A3-B14-C5; A3-B14-C6; A3-B14-C7; A3-B14-C8; A3-B14-C9;A3-B14-C10; A3-B14-C11; A3-B14-C12; A3-B14-C13; A3-B14-C14; A3-B14-C15;A3-B14-C16; A3-B14-C17; A3-B14-C18; A3-B14-C19; A3-B14-C20; A3-B14-C21;A3-B14-C22; A3-B14-C23; A3-B14-C24; A3-B14-C25; A3-B14-C26; A3-B14-C27;A3-B14-C28; A3-B14-C29; A3-B14-C30; A3-B14-C31; A3-B14-C32; A3-B14-C33;A3-B14-C34; A3-B14-C35; A3-B14-C36; A3-B14-C37; A3-B14-C38; A3-B14-C39;A3-B14-C40; A3-B14-C41; A3-B14-C42; A3-B14-C43; A3-B14-C44; A3-B14-C45;A3-B14-C46; A4-B14-C1; A4-B14-C2; A4-B14-C3; A4-B14-C4; A4-B14-C5;A4-B14-C6; A4-B14-C7; A4-B14-C8; A4-B14-C9; A4-B14-C10; A4-B14-C11;A4-B14-C12; A4-B14-C13; A4-B14-C14; A4-B14-C15; A4-B14-C16; A4-B14-C17;A4-B14-C18; A4-B14-C19; A4-B14-C20; A4-B14-C21; A4-B14-C22; A4-B14-C23;A4-B14-C24; A4-B14-C25; A4-B14-C26; A4-B14-C27; A4-B14-C28; A4-B14-C29;A4-B14-C30; A4-B14-C31; A4-B14-C32; A4-B14-C33; A4-B14-C34; A4-B14-C35;A4-B14-C36; A4-B14-C37; A4-B14-C38; A4-B14-C39; A4-B14-C40; A4-B14-C41;A4-B14-C42; A4-B14-C43; A4-B14-C44; A4-B14-C45; A4-B14-C46; A5-B14-C1;A5-B14-C2; A5-B14-C3; A5-B14-C4; A5-B14-C5; A5-B14-C6; A5-B14-C7;A5-B14-C8; A5-B14-C9; A5-B14-C10; A5-B14-C11; A5-B14-C12; A5-B14-C13;A5-B14-C14; A5-B14-C15; A5-B14-C16; A5-B14-C17; A5-B14-C18; A5-B14-C19;A5-B14-C20; A5-B14-C21; A5-B14-C22; A5-B14-C23; A5-B14-C24; A5-B14-C25;A5-B14-C26; A5-B14-C27; A5-B14-C28; A5-B14-C29; A5-B14-C30; A5-B14-C31;A5-B14-C32; A5-B14-C33; A5-B14-C34; A5-B14-C35; A5-B14-C36; A5-B14-C37;A5-B14-C38; A5-B14-C39; A5-B14-C40; A5-B14-C41; A5-B14-C42; A5-B14-C43;A5-B14-C44; A5-B14-C45; A5-B14-C46; A6-B14-C1; A6-B14-C2; A6-B14-C3;A6-B14-C4; A6-B14-C5; A6-B14-C6; A6-B14-C7; A6-B14-C8; A6-B14-C9;A6-B14-C10; A6-B14-C11; A6-B14-C12; A6-B14-C13; A6-B14-C14; A6-B14-C15;A6-B14-C16; A6-B14-C17; A6-B14-C18; A6-B14-C19; A6-B14-C20; A6-B14-C21;A6-B14-C22; A6-B14-C23; A6-B14-C24; A6-B14-C25; A6-B14-C26; A6-B14-C27;A6-B14-C28; A6-B14-C29; A6-B14-C30; A6-B14-C31; A6-B14-C32; A6-B14-C33;A6-B14-C34; A6-B14-C35; A6-B14-C36; A6-B14-C37; A6-B14-C38; A6-B14-C39;A6-B14-C40; A6-B14-C41; A6-B14-C42; A6-B14-C43; A6-B14-C44; A6-B14-C45;A6-B14-C46; A7-B14-C1; A7-B14-C2; A7-B14-C3; A7-B14-C4; A7-B14-C5;A7-B14-C6; A7-B14-C7; A7-B14-C8; A7-B14-C9; A7-B14-C10; A7-B14-C11;A7-B14-C12; A7-B14-C13; A7-B14-C14; A7-B14-C15; A7-B14-C16; A7-B14-C17;A7-B14-C18; A7-B14-C19; A7-B14-C20; A7-B14-C21; A7-B14-C22; A7-B14-C23;A7-B14-C24; A7-B14-C25; A7-B14-C26; A7-B14-C27; A7-B14-C28; A7-B14-C29;A7-B14-C30; A7-B14-C31; A7-B14-C32; A7-B14-C33; A7-B14-C34; A7-B14-C35;A7-B14-C36; A7-B14-C37; 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A9-B14-C32; A9-B14-C33;A9-B14-C34; A9-B14-C35; A9-B14-C36; A9-B14-C37; A9-B14-C38; A9-B14-C39;A9-B14-C40; A9-B14-C41; A9-B14-C42; A9-B14-C43; A9-B14-C44; A9-B14-C45;A9-B14-C46; A10-B14-C1; A10-B14-C2; A10-B14-C3; A10-B14-C4; A10-B14-C5;A10-B14-C6; A10-B14-C7; A10-B14-C8; A10-B14-C9; A10-B14-C10;A10-B14-C11; A10-B14-C12; A10-B14-C13; A10-B14-C14; A10-B14-C15;A10-B14-C16; A10-B14-C17; A10-B14-C18; A10-B14-C19; A10-B14-C20;A10-B14-C21; A10-B14-C22; A10-B14-C23; A10-B14-C24; A10-B14-C25;A10-B14-C26; A10-B14-C27; A10-B14-C28; A10-B14-C29; A10-B14-C30;A10-B14-C31; A10-B14-C32; A10-B14-C33; A10-B14-C34; A10-B14-C35;A10-B14-C36; A10-B14-C37; A10-B14-C38; A10-B14-C39; A10-B14-C40;A10-B14-C41; A10-B14-C42; A10-B14-C43; A10-B14-C44; A10-B14-C45;A10-B14-C46; A11-B14-C1; A11-B14-C2; A11-B14-C3; A11-B14-C4; A11-B14-C5;A11-B14-C6; A11-B14-C7; A11-B14-C8; A11-B14-C9; A11-B14-C10;A11-B14-C11; A11-B14-C12; A11-B14-C13; A11-B14-C14; A11-B14-C15;A11-B14-C16; A11-B14-C17; A11-B14-C18; A11-B14-C19; A11-B14-C20;A11-B14-C21; 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A13-B14-C10;A13-B14-C11; A13-B14-C12; A13-B14-C13; A13-B14-C14; A13-B14-C15;A13-B14-C16; A13-B14-C17; A13-B14-C18; A13-B14-C19; A13-B14-C20;A13-B14-C21; A13-B14-C22; A13-B14-C23; A13-B14-C24; A13-B14-C25;A13-B14-C26; A13-B14-C27; A13-B14-C28; A13-B14-C29; A13-B14-C30;A13-B14-C31; A13-B14-C32; A13-B14-C33; A13-B14-C34; A13-B14-C35;A13-B14-C36; A13-B14-C37; A13-B14-C38; A13-B14-C39; A13-B14-C40;A13-B14-C41; A13-B14-C42; A13-B14-C43; A13-B14-C44; A13-B14-C45;A13-B14-C46; A14-B14-C1; A14-B14-C2; A14-B14-C3; A14-B14-C4; A14-B14-C5;A14-B14-C6; A14-B14-C7; A14-B14-C8; A14-B14-C9; A14-B14-C10;A14-B14-C11; A14-B14-C12; A14-B14-C13; A14-B14-C14; A14-B14-C15;A14-B14-C16; A14-B14-C17; A14-B14-C18; A14-B14-C19; A14-B14-C20;A14-B14-C21; A14-B14-C22; A14-B14-C23; A14-B14-C24; A14-B14-C25;A14-B14-C26; A14-B14-C27; A14-B14-C28; A14-B14-C29; A14-B14-C30;A14-B14-C31; A14-B14-C32; A14-B14-C33; A14-B14-C34; A14-B14-C35;A14-B14-C36; A14-B14-C37; A14-B14-C38; A14-B14-C39; A14-B14-C40;A14-B14-C41; A14-B14-C42; A14-B14-C43; A14-B14-C44; A14-B14-C45;A14-B14-C46; A15-B14-C1; A15-B14-C2; A15-B14-C3; A15-B14-C4; A15-B14-C5;A15-B14-C6; A15-B14-C7; A15-B14-C8; A15-B14-C9; A15-B14-C10;A15-B14-C11; A15-B14-C12; A15-B14-C13; A15-B14-C14; A15-B14-C15;A15-B14-C16; A15-B14-C17; A15-B14-C18; A15-B14-C19; A15-B14-C20;A15-B14-C21; A15-B14-C22; A15-B14-C23; A15-B14-C24; A15-B14-C25;A15-B14-C26; A15-B14-C27; A15-B14-C28; A15-B14-C29; A15-B14-C30;A15-B14-C31; A15-B14-C32; A15-B14-C33; A15-B14-C34; A15-B14-C35;A15-B14-C36; A15-B14-C37; A15-B14-C38; A15-B14-C39; A15-B14-C40;A15-B14-C41; A15-B14-C42; A15-B14-C43; A15-B14-C44; A15-B14-C45;A15-B14-C46; A16-B14-C1; A16-B14-C2; A16-B14-C3; A16-B14-C4; A16-B14-C5;A16-B14-C6; A16-B14-C7; A16-B14-C8; A16-B14-C9; A16-B14-C10;A16-B14-C11; A16-B14-C12; A16-B14-C13; A16-B14-C14; A16-B14-C15;A16-B14-C16; A16-B14-C17; A16-B14-C18; A16-B14-C19; A16-B14-C20;A16-B14-C21; A16-B14-C22; A16-B14-C23; A16-B14-C24; A16-B14-C25;A16-B14-C26; A16-B14-C27; A16-B14-C28; A16-B14-C29; A16-B14-C30;A16-B14-C31; A16-B14-C32; A16-B14-C33; A16-B14-C34; A16-B14-C35;A16-B14-C36; A16-B14-C37; A16-B14-C38; A16-B14-C39; A16-B14-C40;A16-B14-C41; A16-B14-C42; A16-B14-C43; A16-B14-C44; A16-B14-C45;A16-B14-C46; A17-B14-C1; A17-B14-C2; A17-B14-C3; A17-B14-C4; A17-B14-C5;A17-B14-C6; A17-B14-C7; A17-B14-C8; A17-B14-C9; A17-B14-C10;A17-B14-C11; A17-B14-C12; A17-B14-C13; A17-B14-C14; A17-B14-C15;A17-B14-C16; A17-B14-C17; A17-B14-C18; A17-B14-C19; A17-B14-C20;A17-B14-C21; A17-B14-C22; A17-B14-C23; A17-B14-C24; A17-B14-C25;A17-B14-C26; A17-B14-C27; A17-B14-C28; A17-B14-C29; A17-B14-C30;A17-B14-C31; A17-B14-C32; A17-B14-C33; A17-B14-C34; A17-B14-C35;A17-B14-C36; A17-B14-C37; A17-B14-C38; A17-B14-C39; A17-B14-C40;A17-B14-C41; A17-B14-C42; A17-B14-C43; A17-B14-C44; A17-B14-C45;A17-B14-C46; A18-B14-C1; A18-B14-C2; A18-B14-C3; A18-B14-C4; A18-B14-C5;A18-B14-C6; A18-B14-C7; A18-B14-C8; A18-B14-C9; A18-B14-C10;A18-B14-C11; A18-B14-C12; A18-B14-C13; A18-B14-C14; A18-B14-C15;A18-B14-C16; A18-B14-C17; A18-B14-C18; A18-B14-C19; A18-B14-C20;A18-B14-C21; A18-B14-C22; A18-B14-C23; A18-B14-C24; A18-B14-C25;A18-B14-C26; A18-B14-C27; A18-B14-C28; A18-B14-C29; A18-B14-C30;A18-B14-C31; A18-B14-C32; A18-B14-C33; A18-B14-C34; A18-B14-C35;A18-B14-C36; A18-B14-C37; A18-B14-C38; A18-B14-C39; A18-B14-C40;A18-B14-C41; A18-B14-C42; A18-B14-C43; A18-B14-C44; A18-B14-C45;A18-B14-C46; A19-B14-C1; A19-B14-C2; A19-B14-C3; A19-B14-C4; A19-B14-C5;A19-B14-C6; A19-B14-C7; A19-B14-C8; A19-B14-C9; A19-B14-C10;A19-B14-C11; A19-B14-C12; A19-B14-C13; A19-B14-C14; A19-B14-C15;A19-B14-C16; A19-B14-C17; A19-B14-C18; A19-B14-C19; A19-B14-C20;A19-B14-C21; A19-B14-C22; A19-B14-C23; A19-B14-C24; A19-B14-C25;A19-B14-C26; A19-B14-C27; A19-B14-C28; A19-B14-C29; A19-B14-C30;A19-B14-C31; A19-B14-C32; A19-B14-C33; A19-B14-C34; A19-B14-C35;A19-B14-C36; A19-B14-C37; A19-B14-C38; A19-B14-C39; A19-B14-C40;A19-B14-C41; A19-B14-C42; A19-B14-C43; A19-B14-C44; A19-B14-C45;A19-B14-C46; A20-B14-C1; A20-B14-C2; A20-B14-C3; A20-B14-C4; A20-B14-C5;A20-B14-C6; A20-B14-C7; A20-B14-C8; A20-B14-C9; A20-B14-C10;A20-B14-C11; A20-B14-C12; A20-B14-C13; A20-B14-C14; A20-B14-C15;A20-B14-C16; A20-B14-C17; A20-B14-C18; A20-B14-C19; A20-B14-C20;A20-B14-C21; A20-B14-C22; A20-B14-C23; A20-B14-C24; A20-B14-C25;A20-B14-C26; A20-B14-C27; A20-B14-C28; A20-B14-C29; A20-B14-C30;A20-B14-C31; A20-B14-C32; A20-B14-C33; A20-B14-C34; A20-B14-C35;A20-B14-C36; A20-B14-C37; A20-B14-C38; A20-B14-C39; A20-B14-C40;A20-B14-C41; A20-B14-C42; A20-B14-C43; A20-B14-C44; A20-B14-C45;A20-B14-C46; A21-B14-C1; A21-B14-C2; A21-B14-C3; A21-B14-C4; A21-B14-C5;A21-B14-C6; A21-B14-C7; A21-B14-C8; A21-B14-C9; A21-B14-C10;A21-B14-C11; A21-B14-C12; A21-B14-C13; A21-B14-C14; A21-B14-C15;A21-B14-C16; A21-B14-C17; A21-B14-C18; A21-B14-C19; A21-B14-C20;A21-B14-C21; A21-B14-C22; A21-B14-C23; A21-B14-C24; A21-B14-C25;A21-B14-C26; A21-B14-C27; A21-B14-C28; A21-B14-C29; A21-B14-C30;A21-B14-C31; A21-B14-C32; A21-B14-C33; A21-B14-C34; A21-B14-C35;A21-B14-C36; A21-B14-C37; A21-B14-C38; A21-B14-C39; A21-B14-C40;A21-B14-C41; A21-B14-C42; A21-B14-C43; A21-B14-C44; A21-B14-C45;A21-B14-C46; A22-B14-C1; A22-B14-C2; A22-B14-C3; A22-B14-C4; A22-B14-C5;A22-B14-C6; A22-B14-C7; A22-B14-C8; A22-B14-C9; A22-B14-C10;A22-B14-C11; A22-B14-C12; A22-B14-C13; A22-B14-C14; A22-B14-C15;A22-B14-C16; A22-B14-C17; A22-B14-C18; A22-B14-C19; A22-B14-C20;A22-B14-C21; A22-B14-C22; A22-B14-C23; A22-B14-C24; A22-B14-C25;A22-B14-C26; A22-B14-C27; A22-B14-C28; A22-B14-C29; A22-B14-C30;A22-B14-C31; A22-B14-C32; A22-B14-C33; A22-B14-C34; A22-B14-C35;A22-B14-C36; A22-B14-C37; A22-B14-C38; A22-B14-C39; A22-B14-C40;A22-B14-C41; A22-B14-C42; A22-B14-C43; A22-B14-C44; A22-B14-C45;A22-B14-C46; A23-B14-C1; A23-B14-C2; A23-B14-C3; A23-B14-C4; A23-B14-C5;A23-B14-C6; A23-B14-C7; A23-B14-C8; A23-B14-C9; A23-B14-C10;A23-B14-C11; A23-B14-C12; A23-B14-C13; A23-B14-C14; A23-B14-C15;A23-B14-C16; A23-B14-C17; A23-B14-C18; A23-B14-C19; A23-B14-C20;A23-B14-C21; A23-B14-C22; A23-B14-C23; A23-B14-C24; A23-B14-C25;A23-B14-C26; A23-B14-C27; A23-B14-C28; A23-B14-C29; A23-B14-C30;A23-B14-C31; A23-B14-C32; A23-B14-C33; A23-B14-C34; A23-B14-C35;A23-B14-C36; A23-B14-C37; A23-B14-C38; A23-B14-C39; A23-B14-C40;A23-B14-C41; A23-B14-C42; A23-B14-C43; A23-B14-C44; A23-B14-C45;A23-B14-C46; A24-B14-C1; A24-B14-C2; A24-B14-C3; A24-B14-C4; A24-B14-C5;A24-B14-C6; A24-B14-C7; A24-B14-C8; A24-B14-C9; A24-B14-C10;A24-B14-C11; A24-B14-C12; A24-B14-C13; A24-B14-C14; A24-B14-C15;A24-B14-C16; A24-B14-C17; A24-B14-C18; A24-B14-C19; A24-B14-C20;A24-B14-C21; A24-B14-C22; A24-B14-C23; A24-B14-C24; A24-B14-C25;A24-B14-C26; A24-B14-C27; A24-B14-C28; A24-B14-C29; A24-B14-C30;A24-B14-C31; A24-B14-C32; A24-B14-C33; A24-B14-C34; A24-B14-C35;A24-B14-C36; A24-B14-C37; A24-B14-C38; A24-B14-C39; A24-B14-C40;A24-B14-C41; A24-B14-C42; A24-B14-C43; A24-B14-C44; A24-B14-C45;A24-B14-C46; A25-B14-C1; A25-B14-C2; A25-B14-C3; A25-B14-C4; A25-B14-C5;A25-B14-C6; A25-B14-C7; A25-B14-C8; A25-B14-C9; A25-B14-C10;A25-B14-C11; A25-B14-C12; A25-B14-C13; A25-B14-C14; A25-B14-C15;A25-B14-C16; A25-B14-C17; A25-B14-C18; A25-B14-C19; A25-B14-C20;A25-B14-C21; A25-B14-C22; A25-B14-C23; A25-B14-C24; A25-B14-C25;A25-B14-C26; A25-B14-C27; A25-B14-C28; A25-B14-C29; A25-B14-C30;A25-B14-C31; A25-B14-C32; A25-B14-C33; A25-B14-C34; A25-B14-C35;A25-B14-C36; A25-B14-C37; A25-B14-C38; A25-B14-C39; A25-B14-C40;A25-B14-C41; A25-B14-C42; A25-B14-C43; A25-B14-C44; A25-B14-C45;A25-B14-C46; A26-B14-C1; A26-B14-C2; A26-B14-C3; A26-B14-C4; A26-B14-C5;A26-B14-C6; A26-B14-C7; A26-B14-C8; A26-B14-C9; A26-B14-C10;A26-B14-C11; A26-B14-C12; A26-B14-C13; A26-B14-C14; A26-B14-C15;A26-B14-C16; A26-B14-C17; A26-B14-C18; A26-B14-C19; A26-B14-C20;A26-B14-C21; A26-B14-C22; A26-B14-C23; A26-B14-C24; A26-B14-C25;A26-B14-C26; A26-B14-C27; A26-B14-C28; A26-B14-C29; A26-B14-C30;A26-B14-C31; A26-B14-C32; A26-B14-C33; A26-B14-C34; A26-B14-C35;A26-B14-C36; A26-B14-C37; A26-B14-C38; A26-B14-C39; A26-B14-C40;A26-B14-C41; A26-B14-C42; A26-B14-C43; A26-B14-C44; A26-B14-C45;A26-B14-C46; A27-B14-C1; A27-B14-C2; A27-B14-C3; A27-B14-C4; A27-B14-C5;A27-B14-C6; A27-B14-C7; A27-B14-C8; A27-B14-C9; A27-B14-C10;A27-B14-C11; A27-B14-C12; A27-B14-C13; A27-B14-C14; A27-B14-C15;A27-B14-C16; A27-B14-C17; A27-B14-C18; A27-B14-C19; A27-B14-C20;A27-B14-C21; A27-B14-C22; A27-B14-C23; A27-B14-C24; A27-B14-C25;A27-B14-C26; A27-B14-C27; A27-B14-C28; A27-B14-C29; A27-B14-C30;A27-B14-C31; A27-B14-C32; A27-B14-C33; A27-B14-C34; A27-B14-C35;A27-B14-C36; A27-B14-C37; A27-B14-C38; A27-B14-C39; A27-B14-C40;A27-B14-C41; A27-B14-C42; A27-B14-C43; A27-B14-C44; A27-B14-C45;A27-B14-C46; A28-B14-C1; A28-B14-C2; A28-B14-C3; A28-B14-C4; A28-B14-C5;A28-B14-C6; A28-B14-C7; A28-B14-C8; A28-B14-C9; A28-B14-C10;A28-B14-C11; A28-B14-C12; A28-B14-C13; A28-B14-C14; A28-B14-C15;A28-B14-C16; A28-B14-C17; A28-B14-C18; A28-B14-C19; A28-B14-C20;A28-B14-C21; A28-B14-C22; A28-B14-C23; A28-B14-C24; A28-B14-C25;A28-B14-C26; A28-B14-C27; A28-B14-C28; A28-B14-C29; A28-B14-C30;A28-B14-C31; A28-B14-C32; A28-B14-C33; A28-B14-C34; A28-B14-C35;A28-B14-C36; A28-B14-C37; A28-B14-C38; A28-B14-C39; A28-B14-C40;A28-B14-C41; A28-B14-C42; A28-B14-C43; A28-B14-C44; A28-B14-C45;A28-B14-C46; A1-B15-C1; A1-B15-C2; A1-B15-C3; A1-B15-C4; A1-B15-C5;A1-B15-C6; A1-B15-C7; A1-B15-C8; A1-B15-C9; A1-B15-C10; A1-B15-C11;A1-B15-C12; A1-B15-C13; A1-B15-C14; A1-B15-C15; A1-B15-C16; A1-B15-C17;A1-B15-C18; A1-B15-C19; A1-B15-C20; A1-B15-C21; A1-B15-C22; A1-B15-C23;A1-B15-C24; A1-B15-C25; A1-B15-C26; A1-B15-C27; A1-B15-C28; A1-B15-C29;A1-B15-C30; A1-B15-C31; A1-B15-C32; A1-B15-C33; A1-B15-C34; A1-B15-C35;A1-B15-C36; A1-B15-C37; A1-B15-C38; A1-B15-C39; A1-B15-C40; A1-B15-C41;A1-B15-C42; A1-B15-C43; A1-B15-C44; A1-B15-C45; A1-B15-C46; A2-B15-C1;A2-B15-C2; A2-B15-C3; A2-B15-C4; A2-B15-C5; A2-B15-C6; A2-B15-C7;A2-B15-C8; A2-B15-C9; A2-B15-C10; A2-B15-C11; A2-B15-C12; A2-B15-C13;A2-B15-C14; A2-B15-C15; A2-B15-C16; A2-B15-C17; A2-B15-C18; A2-B15-C19;A2-B15-C20; A2-B15-C21; A2-B15-C22; A2-B15-C23; A2-B15-C24; A2-B15-C25;A2-B15-C26; A2-B15-C27; A2-B15-C28; A2-B15-C29; A2-B15-C30; A2-B15-C31;A2-B15-C32; A2-B15-C33; A2-B15-C34; A2-B15-C35; A2-B15-C36; A2-B15-C37;A2-B15-C38; A2-B15-C39; A2-B15-C40; A2-B15-C41; A2-B15-C42; A2-B15-C43;A2-B15-C44; A2-B15-C45; A2-B15-C46; A3-B15-C1; A3-B15-C2; A3-B15-C3;A3-B15-C4; A3-B15-C5; A3-B15-C6; A3-B15-C7; A3-B15-C8; A3-B15-C9;A3-B15-C10; A3-B15-C11; A3-B15-C12; A3-B15-C13; A3-B15-C14; A3-B15-C15;A3-B15-C16; A3-B15-C17; A3-B15-C18; A3-B15-C19; A3-B15-C20; A3-B15-C21;A3-B15-C22; A3-B15-C23; A3-B15-C24; A3-B15-C25; A3-B15-C26; A3-B15-C27;A3-B15-C28; A3-B15-C29; A3-B15-C30; A3-B15-C31; A3-B15-C32; A3-B15-C33;A3-B15-C34; A3-B15-C35; A3-B15-C36; A3-B15-C37; A3-B15-C38; A3-B15-C39;A3-B15-C40; A3-B15-C41; A3-B15-C42; A3-B15-C43; A3-B15-C44; A3-B15-C45;A3-B15-C46; A4-B15-C1; A4-B15-C2; A4-B15-C3; A4-B15-C4; A4-B15-C5;A4-B15-C6; A4-B15-C7; A4-B15-C8; A4-B15-C9; A4-B15-C10; A4-B15-C11;A4-B15-C12; A4-B15-C13; A4-B15-C14; A4-B15-C15; A4-B15-C16; A4-B15-C17;A4-B15-C18; A4-B15-C19; A4-B15-C20; A4-B15-C21; A4-B15-C22; A4-B15-C23;A4-B15-C24; A4-B15-C25; A4-B15-C26; A4-B15-C27; A4-B15-C28; A4-B15-C29;A4-B15-C30; A4-B15-C31; A4-B15-C32; A4-B15-C33; A4-B15-C34; A4-B15-C35;A4-B15-C36; A4-B15-C37; A4-B15-C38; A4-B15-C39; A4-B15-C40; A4-B15-C41;A4-B15-C42; A4-B15-C43; A4-B15-C44; A4-B15-C45; A4-B15-C46; A5-B15-C1;A5-B15-C2; A5-B15-C3; A5-B15-C4; A5-B15-C5; A5-B15-C6; A5-B15-C7;A5-B15-C8; A5-B15-C9; A5-B15-C10; A5-B15-C11; A5-B15-C12; A5-B15-C13;A5-B15-C14; A5-B15-C15; A5-B15-C16; A5-B15-C17; A5-B15-C18; A5-B15-C19;A5-B15-C20; A5-B15-C21; A5-B15-C22; A5-B15-C23; A5-B15-C24; A5-B15-C25;A5-B15-C26; A5-B15-C27; A5-B15-C28; A5-B15-C29; A5-B15-C30; A5-B15-C31;A5-B15-C32; A5-B15-C33; A5-B15-C34; A5-B15-C35; A5-B15-C36; A5-B15-C37;A5-B15-C38; A5-B15-C39; A5-B15-C40; A5-B15-C41; A5-B15-C42; A5-B15-C43;A5-B15-C44; A5-B15-C45; A5-B15-C46; A6-B15-C1; A6-B15-C2; A6-B15-C3;A6-B15-C4; A6-B15-C5; A6-B15-C6; A6-B15-C7; A6-B15-C8; A6-B15-C9;A6-B15-C10; A6-B15-C11; A6-B15-C12; A6-B15-C13; A6-B15-C14; A6-B15-C15;A6-B15-C16; A6-B15-C17; A6-B15-C18; A6-B15-C19; A6-B15-C20; A6-B15-C21;A6-B15-C22; A6-B15-C23; A6-B15-C24; A6-B15-C25; A6-B15-C26; A6-B15-C27;A6-B15-C28; A6-B15-C29; A6-B15-C30; A6-B15-C31; A6-B15-C32; A6-B15-C33;A6-B15-C34; A6-B15-C35; A6-B15-C36; A6-B15-C37; A6-B15-C38; A6-B15-C39;A6-B15-C40; A6-B15-C41; A6-B15-C42; A6-B15-C43; A6-B15-C44; A6-B15-C45;A6-B15-C46; A7-B15-C1; A7-B15-C2; A7-B15-C3; A7-B15-C4; A7-B15-C5;A7-B15-C6; A7-B15-C7; A7-B15-C8; A7-B15-C9; A7-B15-C10; A7-B15-C11;A7-B15-C12; A7-B15-C13; A7-B15-C14; A7-B15-C15; A7-B15-C16; A7-B15-C17;A7-B15-C18; A7-B15-C19; A7-B15-C20; A7-B15-C21; A7-B15-C22; A7-B15-C23;A7-B15-C24; A7-B15-C25; A7-B15-C26; A7-B15-C27; A7-B15-C28; A7-B15-C29;A7-B15-C30; A7-B15-C31; A7-B15-C32; A7-B15-C33; A7-B15-C34; A7-B15-C35;A7-B15-C36; A7-B15-C37; A7-B15-C38; A7-B15-C39; A7-B15-C40; A7-B15-C41;A7-B15-C42; A7-B15-C43; A7-B15-C44; A7-B15-C45; A7-B15-C46; A8-B15-C1;A8-B15-C2; A8-B15-C3; A8-B15-C4; A8-B15-C5; A8-B15-C6; A8-B15-C7;A8-B15-C8; A8-B15-C9; A8-B15-C10; A8-B15-C11; A8-B15-C12; A8-B15-C13;A8-B15-C14; A8-B15-C15; A8-B15-C16; A8-B15-C17; A8-B15-C18; A8-B15-C19;A8-B15-C20; A8-B15-C21; A8-B15-C22; A8-B15-C23; A8-B15-C24; A8-B15-C25;A8-B15-C26; A8-B15-C27; A8-B15-C28; A8-B15-C29; A8-B15-C30; A8-B15-C31;A8-B15-C32; A8-B15-C33; A8-B15-C34; A8-B15-C35; A8-B15-C36; A8-B15-C37;A8-B15-C38; A8-B15-C39; A8-B15-C40; A8-B15-C41; A8-B15-C42; A8-B15-C43;A8-B15-C44; A8-B15-C45; A8-B15-C46; A9-B15-C1; A9-B15-C2; A9-B15-C3;A9-B15-C4; A9-B15-C5; A9-B15-C6; A9-B15-C7; A9-B15-C8; A9-B15-C9;A9-B15-C10; A9-B15-C11; A9-B15-C12; A9-B15-C13; A9-B15-C14; A9-B15-C15;A9-B15-C16; A9-B15-C17; A9-B15-C18; A9-B15-C19; A9-B15-C20; A9-B15-C21;A9-B15-C22; A9-B15-C23; A9-B15-C24; A9-B15-C25; A9-B15-C26; A9-B15-C27;A9-B15-C28; A9-B15-C29; A9-B15-C30; A9-B15-C31; A9-B15-C32; A9-B15-C33;A9-B15-C34; A9-B15-C35; A9-B15-C36; A9-B15-C37; A9-B15-C38; A9-B15-C39;A9-B15-C40; A9-B15-C41; A9-B15-C42; A9-B15-C43; A9-B15-C44; A9-B15-C45;A9-B15-C46; A10-B15-C1; A10-B15-C2; A10-B15-C3; A10-B15-C4; A10-B15-C5;A10-B15-C6; A10-B15-C7; A10-B15-C8; A10-B15-C9; A10-B15-C10;A10-B15-C11; A10-B15-C12; A10-B15-C13; A10-B15-C14; A10-B15-C15;A10-B15-C16; A10-B15-C17; A10-B15-C18; A10-B15-C19; A10-B15-C20;A10-B15-C21; A10-B15-C22; A10-B15-C23; A10-B15-C24; A10-B15-C25;A10-B15-C26; A10-B15-C27; A10-B15-C28; A10-B15-C29; A10-B15-C30;A10-B15-C31; A10-B15-C32; A10-B15-C33; A10-B15-C34; A10-B15-C35;A10-B15-C36; A10-B15-C37; A10-B15-C38; A10-B15-C39; A10-B15-C40;A10-B15-C41; A10-B15-C42; A10-B15-C43; A10-B15-C44; A10-B15-C45;A10-B15-C46; A11-B15-C1; A11-B15-C2; A11-B15-C3; A11-B15-C4; A11-B15-C5;A11-B15-C6; A11-B15-C7; A11-B15-C8; A11-B15-C9; A11-B15-C10;A11-B15-C11; A11-B15-C12; A11-B15-C13; A11-B15-C14; A11-B15-C15;A11-B15-C16; A11-B15-C17; A11-B15-C18; A11-B15-C19; A11-B15-C20;A11-B15-C21; A11-B15-C22; A11-B15-C23; A11-B15-C24; A11-B15-C25;A11-B15-C26; A11-B15-C27; A11-B15-C28; A11-B15-C29; A11-B15-C30;A11-B15-C31; A11-B15-C32; A11-B15-C33; A11-B15-C34; A11-B15-C35;A11-B15-C36; A11-B15-C37; A11-B15-C38; A11-B15-C39; A11-B15-C40;A11-B15-C41; A11-B15-C42; A11-B15-C43; A11-B15-C44; A11-B15-C45;A11-B15-C46; A12-B15-C1; A12-B15-C2; A12-B15-C3; A12-B15-C4; A12-B15-C5;A12-B15-C6; A12-B15-C7; A12-B15-C8; A12-B15-C9; A12-B15-C10;A12-B15-C11; A12-B15-C12; A12-B15-C13; A12-B15-C14; A12-B15-C15;A12-B15-C16; A12-B15-C17; A12-B15-C18; A12-B15-C19; A12-B15-C20;A12-B15-C21; A12-B15-C22; A12-B15-C23; A12-B15-C24; A12-B15-C25;A12-B15-C26; A12-B15-C27; A12-B15-C28; A12-B15-C29; A12-B15-C30;A12-B15-C31; A12-B15-C32; A12-B15-C33; A12-B15-C34; A12-B15-C35;A12-B15-C36; A12-B15-C37; A12-B15-C38; A12-B15-C39; A12-B15-C40;A12-B15-C41; A12-B15-C42; A12-B15-C43; A12-B15-C44; A12-B15-C45;A12-B15-C46; A13-B15-C1; A13-B15-C2; A13-B15-C3; A13-B15-C4; A13-B15-C5;A13-B15-C6; A13-B15-C7; A13-B15-C8; A13-B15-C9; A13-B15-C10;A13-B15-C11; A13-B15-C12; A13-B15-C13; A13-B15-C14; A13-B15-C15;A13-B15-C16; A13-B15-C17; A13-B15-C18; A13-B15-C19; A13-B15-C20;A13-B15-C21; A13-B15-C22; A13-B15-C23; A13-B15-C24; A13-B15-C25;A13-B15-C26; A13-B15-C27; A13-B15-C28; A13-B15-C29; A13-B15-C30;A13-B15-C31; A13-B15-C32; A13-B15-C33; A13-B15-C34; A13-B15-C35;A13-B15-C36; A13-B15-C37; A13-B15-C38; A13-B15-C39; A13-B15-C40;A13-B15-C41; A13-B15-C42; A13-B15-C43; A13-B15-C44; A13-B15-C45;A13-B15-C46; A14-B15-C1; A14-B15-C2; A14-B15-C3; A14-B15-C4; A14-B15-C5;A14-B15-C6; A14-B15-C7; A14-B15-C8; A14-B15-C9; A14-B15-C10;A14-B15-C11; A14-B15-C12; A14-B15-C13; A14-B15-C14; A14-B15-C15;A14-B15-C16; A14-B15-C17; A14-B15-C18; A14-B15-C19; A14-B15-C20;A14-B15-C21; A14-B15-C22; A14-B15-C23; A14-B15-C24; A14-B15-C25;A14-B15-C26; A14-B15-C27; A14-B15-C28; A14-B15-C29; A14-B15-C30;A14-B15-C31; A14-B15-C32; A14-B15-C33; A14-B15-C34; A14-B15-C35;A14-B15-C36; A14-B15-C37; A14-B15-C38; A14-B15-C39; A14-B15-C40;A14-B15-C41; A14-B15-C42; A14-B15-C43; A14-B15-C44; A14-B15-C45;A14-B15-C46; A15-B15-C1; A15-B15-C2; A15-B15-C3; A15-B15-C4; A15-B15-C5;A15-B15-C6; A15-B15-C7; A15-B15-C8; A15-B15-C9; A15-B15-C10;A15-B15-C11; A15-B15-C12; A15-B15-C13; A15-B15-C14; A15-B15-C15;A15-B15-C16; A15-B15-C17; A15-B15-C18; A15-B15-C19; A15-B15-C20;A15-B15-C21; A15-B15-C22; A15-B15-C23; A15-B15-C24; A15-B15-C25;A15-B15-C26; A15-B15-C27; A15-B15-C28; A15-B15-C29; A15-B15-C30;A15-B15-C31; A15-B15-C32; A15-B15-C33; A15-B15-C34; A15-B15-C35;A15-B15-C36; A15-B15-C37; A15-B15-C38; A15-B15-C39; A15-B15-C40;A15-B15-C41; A15-B15-C42; A15-B15-C43; A15-B15-C44; A15-B15-C45;A15-B15-C46; A16-B15-C1; A16-B15-C2; A16-B15-C3; A16-B15-C4; A16-B15-C5;A16-B15-C6; A16-B15-C7; A16-B15-C8; A16-B15-C9; A16-B15-C10;A16-B15-C11; A16-B15-C12; A16-B15-C13; A16-B15-C14; A16-B15-C15;A16-B15-C16; A16-B15-C17; A16-B15-C18; A16-B15-C19; A16-B15-C20;A16-B15-C21; A16-B15-C22; A16-B15-C23; A16-B15-C24; A16-B15-C25;A16-B15-C26; A16-B15-C27; A16-B15-C28; A16-B15-C29; A16-B15-C30;A16-B15-C31; A16-B15-C32; A16-B15-C33; A16-B15-C34; A16-B15-C35;A16-B15-C36; A16-B15-C37; A16-B15-C38; A16-B15-C39; A16-B15-C40;A16-B15-C41; A16-B15-C42; A16-B15-C43; A16-B15-C44; A16-B15-C45;A16-B15-C46; A17-B15-C1; A17-B15-C2; A17-B15-C3; A17-B15-C4; A17-B15-C5;A17-B15-C6; A17-B15-C7; A17-B15-C8; A17-B15-C9; A17-B15-C10;A17-B15-C11; A17-B15-C12; A17-B15-C13; A17-B15-C14; A17-B15-C15;A17-B15-C16; A17-B15-C17; A17-B15-C18; A17-B15-C19; A17-B15-C20;A17-B15-C21; A17-B15-C22; A17-B15-C23; A17-B15-C24; A17-B15-C25;A17-B15-C26; A17-B15-C27; A17-B15-C28; A17-B15-C29; A17-B15-C30;A17-B15-C31; A17-B15-C32; A17-B15-C33; A17-B15-C34; A17-B15-C35;A17-B15-C36; A17-B15-C37; A17-B15-C38; A17-B15-C39; A17-B15-C40;A17-B15-C41; A17-B15-C42; A17-B15-C43; A17-B15-C44; A17-B15-C45;A17-B15-C46; A18-B15-C1; A18-B15-C2; A18-B15-C3; A18-B15-C4; A18-B15-C5;A18-B15-C6; A18-B15-C7; A18-B15-C8; A18-B15-C9; A18-B15-C10;A18-B15-C11; A18-B15-C12; A18-B15-C13; A18-B15-C14; A18-B15-C15;A18-B15-C16; A18-B15-C17; A18-B15-C18; A18-B15-C19; A18-B15-C20;A18-B15-C21; A18-B15-C22; A18-B15-C23; A18-B15-C24; A18-B15-C25;A18-B15-C26; A18-B15-C27; A18-B15-C28; A18-B15-C29; A18-B15-C30;A18-B15-C31; A18-B15-C32; A18-B15-C33; A18-B15-C34; A18-B15-C35;A18-B15-C36; A18-B15-C37; A18-B15-C38; A18-B15-C39; A18-B15-C40;A18-B15-C41; A18-B15-C42; A18-B15-C43; A18-B15-C44; A18-B15-C45;A18-B15-C46; A19-B15-C1; A19-B15-C2; A19-B15-C3; A19-B15-C4; A19-B15-C5;A19-B15-C6; A19-B15-C7; A19-B15-C8; A19-B15-C9; A19-B15-C10;A19-B15-C11; A19-B15-C12; A19-B15-C13; A19-B15-C14; A19-B15-C15;A19-B15-C16; A19-B15-C17; A19-B15-C18; A19-B15-C19; A19-B15-C20;A19-B15-C21; A19-B15-C22; A19-B15-C23; A19-B15-C24; A19-B15-C25;A19-B15-C26; A19-B15-C27; A19-B15-C28; A19-B15-C29; A19-B15-C30;A19-B15-C31; A19-B15-C32; A19-B15-C33; A19-B15-C34; A19-B15-C35;A19-B15-C36; A19-B15-C37; A19-B15-C38; A19-B15-C39; A19-B15-C40;A19-B15-C41; A19-B15-C42; A19-B15-C43; A19-B15-C44; A19-B15-C45;A19-B15-C46; A20-B15-C1; A20-B15-C2; A20-B15-C3; A20-B15-C4; A20-B15-C5;A20-B15-C6; A20-B15-C7; A20-B15-C8; A20-B15-C9; A20-B15-C10;A20-B15-C11; A20-B15-C12; A20-B15-C13; A20-B15-C14; A20-B15-C15;A20-B15-C16; A20-B15-C17; A20-B15-C18; A20-B15-C19; A20-B15-C20;A20-B15-C21; A20-B15-C22; A20-B15-C23; A20-B15-C24; A20-B15-C25;A20-B15-C26; A20-B15-C27; A20-B15-C28; A20-B15-C29; A20-B15-C30;A20-B15-C31; A20-B15-C32; A20-B15-C33; A20-B15-C34; A20-B15-C35;A20-B15-C36; A20-B15-C37; A20-B15-C38; A20-B15-C39; A20-B15-C40;A20-B15-C41; A20-B15-C42; A20-B15-C43; A20-B15-C44; A20-B15-C45;A20-B15-C46; A21-B15-C1; A21-B15-C2; A21-B15-C3; A21-B15-C4; A21-B15-C5;A21-B15-C6; A21-B15-C7; A21-B15-C8; A21-B15-C9; A21-B15-C10;A21-B15-C11; A21-B15-C12; A21-B15-C13; A21-B15-C14; A21-B15-C15;A21-B15-C16; A21-B15-C17; A21-B15-C18; A21-B15-C19; A21-B15-C20;A21-B15-C21; A21-B15-C22; A21-B15-C23; A21-B15-C24; A21-B15-C25;A21-B15-C26; A21-B15-C27; A21-B15-C28; A21-B15-C29; A21-B15-C30;A21-B15-C31; A21-B15-C32; A21-B15-C33; A21-B15-C34; A21-B15-C35;A21-B15-C36; A21-B15-C37; A21-B15-C38; A21-B15-C39; A21-B15-C40;A21-B15-C41; A21-B15-C42; A21-B15-C43; A21-B15-C44; A21-B15-C45;A21-B15-C46; A22-B15-C1; A22-B15-C2; A22-B15-C3; A22-B15-C4; A22-B15-C5;A22-B15-C6; A22-B15-C7; A22-B15-C8; A22-B15-C9; A22-B15-C10;A22-B15-C11; A22-B15-C12; A22-B15-C13; A22-B15-C14; A22-B15-C15;A22-B15-C16; A22-B15-C17; A22-B15-C18; A22-B15-C19; A22-B15-C20;A22-B15-C21; A22-B15-C22; A22-B15-C23; A22-B15-C24; A22-B15-C25;A22-B15-C26; A22-B15-C27; A22-B15-C28; A22-B15-C29; A22-B15-C30;A22-B15-C31; A22-B15-C32; A22-B15-C33; A22-B15-C34; A22-B15-C35;A22-B15-C36; A22-B15-C37; A22-B15-C38; A22-B15-C39; A22-B15-C40;A22-B15-C41; A22-B15-C42; A22-B15-C43; A22-B15-C44; A22-B15-C45;A22-B15-C46; A23-B15-C1; A23-B15-C2; A23-B15-C3; A23-B15-C4; A23-B15-C5;A23-B15-C6; A23-B15-C7; A23-B15-C8; A23-B15-C9; A23-B15-C10;A23-B15-C11; A23-B15-C12; A23-B15-C13; A23-B15-C14; A23-B15-C15;A23-B15-C16; A23-B15-C17; A23-B15-C18; A23-B15-C19; A23-B15-C20;A23-B15-C21; A23-B15-C22; A23-B15-C23; A23-B15-C24; A23-B15-C25;A23-B15-C26; A23-B15-C27; A23-B15-C28; A23-B15-C29; A23-B15-C30;A23-B15-C31; A23-B15-C32; A23-B15-C33; A23-B15-C34; A23-B15-C35;A23-B15-C36; A23-B15-C37; A23-B15-C38; A23-B15-C39; A23-B15-C40;A23-B15-C41; A23-B15-C42; A23-B15-C43; A23-B15-C44; A23-B15-C45;A23-B15-C46; A24-B15-C1; A24-B15-C2; A24-B15-C3; A24-B15-C4; A24-B15-C5;A24-B15-C6; A24-B15-C7; A24-B15-C8; A24-B15-C9; A24-B15-C10;A24-B15-C11; A24-B15-C12; A24-B15-C13; A24-B15-C14; A24-B15-C15;A24-B15-C16; A24-B15-C17; A24-B15-C18; A24-B15-C19; A24-B15-C20;A24-B15-C21; A24-B15-C22; A24-B15-C23; A24-B15-C24; A24-B15-C25;A24-B15-C26; A24-B15-C27; A24-B15-C28; A24-B15-C29; A24-B15-C30;A24-B15-C31; A24-B15-C32; A24-B15-C33; A24-B15-C34; A24-B15-C35;A24-B15-C36; A24-B15-C37; A24-B15-C38; A24-B15-C39; A24-B15-C40;A24-B15-C41; A24-B15-C42; A24-B15-C43; A24-B15-C44; A24-B15-C45;A24-B15-C46; A25-B15-C1; A25-B15-C2; A25-B15-C3; A25-B15-C4; A25-B15-C5;A25-B15-C6; A25-B15-C7; A25-B15-C8; A25-B15-C9; A25-B15-C10;A25-B15-C11; A25-B15-C12; A25-B15-C13; A25-B15-C14; A25-B15-C15;A25-B15-C16; A25-B15-C17; A25-B15-C18; A25-B15-C19; A25-B15-C20;A25-B15-C21; A25-B15-C22; A25-B15-C23; A25-B15-C24; A25-B15-C25;A25-B15-C26; A25-B15-C27; A25-B15-C28; A25-B15-C29; A25-B15-C30;A25-B15-C31; A25-B15-C32; A25-B15-C33; A25-B15-C34; A25-B15-C35;A25-B15-C36; A25-B15-C37; A25-B15-C38; A25-B15-C39; A25-B15-C40;A25-B15-C41; A25-B15-C42; A25-B15-C43; A25-B15-C44; A25-B15-C45;A25-B15-C46; A26-B15-C1; A26-B15-C2; A26-B15-C3; A26-B15-C4; A26-B15-C5;A26-B15-C6; A26-B15-C7; A26-B15-C8; A26-B15-C9; A26-B15-C10;A26-B15-C11; A26-B15-C12; A26-B15-C13; A26-B15-C14; A26-B15-C15;A26-B15-C16; A26-B15-C17; A26-B15-C18; A26-B15-C19; A26-B15-C20;A26-B15-C21; A26-B15-C22; A26-B15-C23; A26-B15-C24; A26-B15-C25;A26-B15-C26; A26-B15-C27; A26-B15-C28; A26-B15-C29; A26-B15-C30;A26-B15-C31; A26-B15-C32; A26-B15-C33; A26-B15-C34; A26-B15-C35;A26-B15-C36; A26-B15-C37; A26-B15-C38; A26-B15-C39; A26-B15-C40;A26-B15-C41; A26-B15-C42; A26-B15-C43; A26-B15-C44; A26-B15-C45;A26-B15-C46; A27-B15-C1; A27-B15-C2; A27-B15-C3; A27-B15-C4; A27-B15-C5;A27-B15-C6; A27-B15-C7; A27-B15-C8; A27-B15-C9; A27-B15-C10;A27-B15-C11; A27-B15-C12; A27-B15-C13; A27-B15-C14; A27-B15-C15;A27-B15-C16; A27-B15-C17; A27-B15-C18; A27-B15-C19; A27-B15-C20;A27-B15-C21; A27-B15-C22; A27-B15-C23; A27-B15-C24; A27-B15-C25;A27-B15-C26; A27-B15-C27; A27-B15-C28; A27-B15-C29; A27-B15-C30;A27-B15-C31; A27-B15-C32; A27-B15-C33; A27-B15-C34; A27-B15-C35;A27-B15-C36; A27-B15-C37; A27-B15-C38; A27-B15-C39; A27-B15-C40;A27-B15-C41; A27-B15-C42; A27-B15-C43; A27-B15-C44; A27-B15-C45;A27-B15-C46; A28-B15-C1; A28-B15-C2; A28-B15-C3; A28-B15-C4; A28-B15-C5;A28-B15-C6; A28-B15-C7; A28-B15-C8; A28-B15-C9; A28-B15-C10;A28-B15-C11; A28-B15-C12; A28-B15-C13; A28-B15-C14; A28-B15-C15;A28-B15-C16; A28-B15-C17; A28-B15-C18; A28-B15-C19; A28-B15-C20;A28-B15-C21; A28-B15-C22; A28-B15-C23; A28-B15-C24; A28-B15-C25;A28-B15-C26; A28-B15-C27; A28-B15-C28; A28-B15-C29; A28-B15-C30;A28-B15-C31; A28-B15-C32; A28-B15-C33; A28-B15-C34; A28-B15-C35;A28-B15-C36; A28-B15-C37; A28-B15-C38; A28-B15-C39; A28-B15-C40;A28-B15-C41; A28-B15-C42; A28-B15-C43; A28-B15-C44; A28-B15-C45;A28-B15-C46; A1-B16-C1; A1-B16-C2; A1-B16-C3; A1-B16-C4; A1-B16-C5;A1-B16-C6; A1-B16-C7; A1-B16-C8; A1-B16-C9; A1-B16-C10; A1-B16-C11;A1-B16-C12; A1-B16-C13; A1-B16-C14; A1-B16-C15; A1-B16-C16; A1-B16-C17;A1-B16-C18; A1-B16-C19; A1-B16-C20; A1-B16-C21; A1-B16-C22; A1-B16-C23;A1-B16-C24; A1-B16-C25; A1-B16-C26; A1-B16-C27; A1-B16-C28; A1-B16-C29;A1-B16-C30; A1-B16-C31; A1-B16-C32; A1-B16-C33; A1-B16-C34; A1-B16-C35;A1-B16-C36; A1-B16-C37; A1-B16-C38; A1-B16-C39; A1-B16-C40; A1-B16-C41;A1-B16-C42; A1-B16-C43; A1-B16-C44; A1-B16-C45; A1-B16-C46; A2-B16-C1;A2-B16-C2; A2-B16-C3; A2-B16-C4; A2-B16-C5; A2-B16-C6; A2-B16-C7;A2-B16-C8; A2-B16-C9; A2-B16-C10; A2-B16-C11; A2-B16-C12; A2-B16-C13;A2-B16-C14; A2-B16-C15; A2-B16-C16; A2-B16-C17; A2-B16-C18; A2-B16-C19;A2-B16-C20; A2-B16-C21; A2-B16-C22; A2-B16-C23; A2-B16-C24; A2-B16-C25;A2-B16-C26; A2-B16-C27; A2-B16-C28; A2-B16-C29; A2-B16-C30; A2-B16-C31;A2-B16-C32; A2-B16-C33; A2-B16-C34; A2-B16-C35; A2-B16-C36; A2-B16-C37;A2-B16-C38; A2-B16-C39; A2-B16-C40; A2-B16-C41; A2-B16-C42; A2-B16-C43;A2-B16-C44; A2-B16-C45; A2-B16-C46; A3-B16-C1; A3-B16-C2; A3-B16-C3;A3-B16-C4; A3-B16-C5; A3-B16-C6; A3-B16-C7; A3-B16-C8; A3-B16-C9;A3-B16-C10; A3-B16-C11; A3-B16-C12; A3-B16-C13; A3-B16-C14; A3-B16-C15;A3-B16-C16; A3-B16-C17; A3-B16-C18; A3-B16-C19; A3-B16-C20; A3-B16-C21;A3-B16-C22; A3-B16-C23; A3-B16-C24; A3-B16-C25; A3-B16-C26; A3-B16-C27;A3-B16-C28; A3-B16-C29; A3-B16-C30; A3-B16-C31; A3-B16-C32; A3-B16-C33;A3-B16-C34; A3-B16-C35; A3-B16-C36; A3-B16-C37; A3-B16-C38; A3-B16-C39;A3-B16-C40; A3-B16-C41; A3-B16-C42; A3-B16-C43; A3-B16-C44; A3-B16-C45;A3-B16-C46; A4-B16-C1; A4-B16-C2; A4-B16-C3; A4-B16-C4; A4-B16-C5;A4-B16-C6; A4-B16-C7; A4-B16-C8; A4-B16-C9; A4-B16-C10; A4-B16-C11;A4-B16-C12; A4-B16-C13; A4-B16-C14; A4-B16-C15; A4-B16-C16; A4-B16-C17;A4-B16-C18; A4-B16-C19; A4-B16-C20; A4-B16-C21; A4-B16-C22; A4-B16-C23;A4-B16-C24; A4-B16-C25; A4-B16-C26; A4-B16-C27; A4-B16-C28; A4-B16-C29;A4-B16-C30; A4-B16-C31; A4-B16-C32; A4-B16-C33; A4-B16-C34; A4-B16-C35;A4-B16-C36; A4-B16-C37; A4-B16-C38; A4-B16-C39; A4-B16-C40; A4-B16-C41;A4-B16-C42; A4-B16-C43; A4-B16-C44; A4-B16-C45; A4-B16-C46; A5-B16-C1;A5-B16-C2; A5-B16-C3; A5-B16-C4; A5-B16-C5; A5-B16-C6; A5-B16-C7;A5-B16-C8; A5-B16-C9; A5-B16-C10; A5-B16-C11; A5-B16-C12; A5-B16-C13;A5-B16-C14; A5-B16-C15; A5-B16-C16; A5-B16-C17; A5-B16-C18; A5-B16-C19;A5-B16-C20; A5-B16-C21; A5-B16-C22; A5-B16-C23; A5-B16-C24; A5-B16-C25;A5-B16-C26; A5-B16-C27; A5-B16-C28; A5-B16-C29; A5-B16-C30; A5-B16-C31;A5-B16-C32; A5-B16-C33; A5-B16-C34; A5-B16-C35; A5-B16-C36; A5-B16-C37;A5-B16-C38; A5-B16-C39; A5-B16-C40; A5-B16-C41; A5-B16-C42; A5-B16-C43;A5-B16-C44; A5-B16-C45; A5-B16-C46; A6-B16-C1; A6-B16-C2; A6-B16-C3;A6-B16-C4; A6-B16-C5; A6-B16-C6; A6-B16-C7; A6-B16-C8; A6-B16-C9;A6-B16-C10; A6-B16-C11; A6-B16-C12; A6-B16-C13; A6-B16-C14; A6-B16-C15;A6-B16-C16; A6-B16-C17; A6-B16-C18; A6-B16-C19; A6-B16-C20; A6-B16-C21;A6-B16-C22; A6-B16-C23; A6-B16-C24; A6-B16-C25; A6-B16-C26; A6-B16-C27;A6-B16-C28; A6-B16-C29; A6-B16-C30; A6-B16-C31; A6-B16-C32; A6-B16-C33;A6-B16-C34; A6-B16-C35; A6-B16-C36; A6-B16-C37; A6-B16-C38; A6-B16-C39;A6-B16-C40; A6-B16-C41; A6-B16-C42; A6-B16-C43; A6-B16-C44; A6-B16-C45;A6-B16-C46; A7-B16-C1; A7-B16-C2; A7-B16-C3; A7-B16-C4; A7-B16-C5;A7-B16-C6; A7-B16-C7; A7-B16-C8; A7-B16-C9; A7-B16-C10; A7-B16-C11;A7-B16-C12; A7-B16-C13; A7-B16-C14; A7-B16-C15; A7-B16-C16; A7-B16-C17;A7-B16-C18; A7-B16-C19; A7-B16-C20; A7-B16-C21; A7-B16-C22; A7-B16-C23;A7-B16-C24; A7-B16-C25; A7-B16-C26; A7-B16-C27; A7-B16-C28; A7-B16-C29;A7-B16-C30; A7-B16-C31; A7-B16-C32; A7-B16-C33; A7-B16-C34; A7-B16-C35;A7-B16-C36; A7-B16-C37; A7-B16-C38; A7-B16-C39; A7-B16-C40; A7-B16-C41;A7-B16-C42; A7-B16-C43; A7-B16-C44; A7-B16-C45; A7-B16-C46; A8-B16-C1;A8-B16-C2; A8-B16-C3; A8-B16-C4; A8-B16-C5; A8-B16-C6; A8-B16-C7;A8-B16-C8; A8-B16-C9; A8-B16-C10; A8-B16-C11; A8-B16-C12; A8-B16-C13;A8-B16-C14; A8-B16-C15; A8-B16-C16; A8-B16-C17; A8-B16-C18; A8-B16-C19;A8-B16-C20; A8-B16-C21; A8-B16-C22; A8-B16-C23; A8-B16-C24; A8-B16-C25;A8-B16-C26; A8-B16-C27; A8-B16-C28; A8-B16-C29; A8-B16-C30; A8-B16-C31;A8-B16-C32; A8-B16-C33; A8-B16-C34; A8-B16-C35; A8-B16-C36; A8-B16-C37;A8-B16-C38; A8-B16-C39; A8-B16-C40; 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A10-B16-C33; A10-B16-C34; A10-B16-C35;A10-B16-C36; A10-B16-C37; A10-B16-C38; A10-B16-C39; A10-B16-C40;A10-B16-C41; A10-B16-C42; A10-B16-C43; A10-B16-C44; A10-B16-C45;A10-B16-C46; A11-B16-C1; A11-B16-C2; A11-B16-C3; A11-B16-C4; A11-B16-C5;A11-B16-C6; A11-B16-C7; A11-B16-C8; A11-B16-C9; A11-B16-C10;A11-B16-C11; A11-B16-C12; A11-B16-C13; A11-B16-C14; A11-B16-C15;A11-B16-C16; A11-B16-C17; A11-B16-C18; A11-B16-C19; A11-B16-C20;A11-B16-C21; A11-B16-C22; A11-B16-C23; A11-B16-C24; A11-B16-C25;A11-B16-C26; A11-B16-C27; A11-B16-C28; A11-B16-C29; A11-B16-C30;A11-B16-C31; A11-B16-C32; A11-B16-C33; A11-B16-C34; A11-B16-C35;A11-B16-C36; A11-B16-C37; A11-B16-C38; A11-B16-C39; A11-B16-C40;A11-B16-C41; A11-B16-C42; A11-B16-C43; A11-B16-C44; A11-B16-C45;A11-B16-C46; A12-B16-C1; A12-B16-C2; A12-B16-C3; A12-B16-C4; A12-B16-C5;A12-B16-C6; A12-B16-C7; A12-B16-C8; A12-B16-C9; A12-B16-C10;A12-B16-C11; A12-B16-C12; A12-B16-C13; A12-B16-C14; A12-B16-C15;A12-B16-C16; A12-B16-C17; A12-B16-C18; A12-B16-C19; A12-B16-C20;A12-B16-C21; 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A28-B16-C7; A28-B16-C8; A28-B16-C9; A28-B16-C10;A28-B16-C11; A28-B16-C12; A28-B16-C13; A28-B16-C14; A28-B16-C15;A28-B16-C16; A28-B16-C17; A28-B16-C18; A28-B16-C19; A28-B16-C20;A28-B16-C21; A28-B16-C22; A28-B16-C23; A28-B16-C24; A28-B16-C25;A28-B16-C26; A28-B16-C27; A28-B16-C28; A28-B16-C29; A28-B16-C30;A28-B16-C31; A28-B16-C32; A28-B16-C33; A28-B16-C34; A28-B16-C35;A28-B16-C36; A28-B16-C37; A28-B16-C38; A28-B16-C39; A28-B16-C40;A28-B16-C41; A28-B16-C42; A28-B16-C43; A28-B16-C44; A28-B16-C45;A28-B16-C46; A1-B17-C1; A1-B17-C2; A1-B17-C3; A1-B17-C4; A1-B17-C5;A1-B17-C6; A1-B17-C7; A1-B17-C8; A1-B17-C9; A1-B17-C10; A1-B17-C11;A1-B17-C12; A1-B17-C13; A1-B17-C14; A1-B17-C15; A1-B17-C16; A1-B17-C17;A1-B17-C18; A1-B17-C19; A1-B17-C20; A1-B17-C21; A1-B17-C22; A1-B17-C23;A1-B17-C24; A1-B17-C25; A1-B17-C26; A1-B17-C27; A1-B17-C28; A1-B17-C29;A1-B17-C30; A1-B17-C31; A1-B17-C32; A1-B17-C33; A1-B17-C34; A1-B17-C35;A1-B17-C36; A1-B17-C37; A1-B17-C38; A1-B17-C39; A1-B17-C40; A1-B17-C41;A1-B17-C42; A1-B17-C43; A1-B17-C44; A1-B17-C45; A1-B17-C46; A2-B17-C1;A2-B17-C2; A2-B17-C3; A2-B17-C4; A2-B17-C5; A2-B17-C6; A2-B17-C7;A2-B17-C8; A2-B17-C9; A2-B17-C10; A2-B17-C11; A2-B17-C12; A2-B17-C13;A2-B17-C14; A2-B17-C15; A2-B17-C16; A2-B17-C17; A2-B17-C18; A2-B17-C19;A2-B17-C20; A2-B17-C21; A2-B17-C22; A2-B17-C23; A2-B17-C24; A2-B17-C25;A2-B17-C26; A2-B17-C27; A2-B17-C28; A2-B17-C29; A2-B17-C30; A2-B17-C31;A2-B17-C32; A2-B17-C33; A2-B17-C34; A2-B17-C35; A2-B17-C36; A2-B17-C37;A2-B17-C38; A2-B17-C39; A2-B17-C40; A2-B17-C41; A2-B17-C42; A2-B17-C43;A2-B17-C44; A2-B17-C45; A2-B17-C46; A3-B17-C1; A3-B17-C2; A3-B17-C3;A3-B17-C4; A3-B17-C5; A3-B17-C6; A3-B17-C7; A3-B17-C8; A3-B17-C9;A3-B17-C10; A3-B17-C11; A3-B17-C12; A3-B17-C13; A3-B17-C14; A3-B17-C15;A3-B17-C16; A3-B17-C17; A3-B17-C18; A3-B17-C19; A3-B17-C20; A3-B17-C21;A3-B17-C22; A3-B17-C23; A3-B17-C24; A3-B17-C25; A3-B17-C26; A3-B17-C27;A3-B17-C28; A3-B17-C29; A3-B17-C30; A3-B17-C31; A3-B17-C32; A3-B17-C33;A3-B17-C34; A3-B17-C35; A3-B17-C36; A3-B17-C37; A3-B17-C38; A3-B17-C39;A3-B17-C40; A3-B17-C41; A3-B17-C42; A3-B17-C43; A3-B17-C44; A3-B17-C45;A3-B17-C46; A4-B17-C1; A4-B17-C2; A4-B17-C3; A4-B17-C4; A4-B17-C5;A4-B17-C6; A4-B17-C7; A4-B17-C8; A4-B17-C9; A4-B17-C10; A4-B17-C11;A4-B17-C12; A4-B17-C13; A4-B17-C14; A4-B17-C15; A4-B17-C16; A4-B17-C17;A4-B17-C18; A4-B17-C19; A4-B17-C20; A4-B17-C21; A4-B17-C22; A4-B17-C23;A4-B17-C24; A4-B17-C25; A4-B17-C26; A4-B17-C27; A4-B17-C28; A4-B17-C29;A4-B17-C30; A4-B17-C31; A4-B17-C32; A4-B17-C33; A4-B17-C34; A4-B17-C35;A4-B17-C36; A4-B17-C37; A4-B17-C38; A4-B17-C39; A4-B17-C40; A4-B17-C41;A4-B17-C42; A4-B17-C43; A4-B17-C44; A4-B17-C45; A4-B17-C46; A5-B17-C1;A5-B17-C2; A5-B17-C3; A5-B17-C4; A5-B17-C5; A5-B17-C6; A5-B17-C7;A5-B17-C8; A5-B17-C9; A5-B17-C10; A5-B17-C11; A5-B17-C12; A5-B17-C13;A5-B17-C14; A5-B17-C15; A5-B17-C16; A5-B17-C17; A5-B17-C18; A5-B17-C19;A5-B17-C20; A5-B17-C21; A5-B17-C22; A5-B17-C23; A5-B17-C24; A5-B17-C25;A5-B17-C26; A5-B17-C27; A5-B17-C28; A5-B17-C29; A5-B17-C30; A5-B17-C31;A5-B17-C32; A5-B17-C33; A5-B17-C34; A5-B17-C35; A5-B17-C36; A5-B17-C37;A5-B17-C38; A5-B17-C39; A5-B17-C40; A5-B17-C41; A5-B17-C42; A5-B17-C43;A5-B17-C44; A5-B17-C45; A5-B17-C46; A6-B17-C1; A6-B17-C2; A6-B17-C3;A6-B17-C4; A6-B17-C5; A6-B17-C6; A6-B17-C7; A6-B17-C8; A6-B17-C9;A6-B17-C10; A6-B17-C11; A6-B17-C12; A6-B17-C13; A6-B17-C14; A6-B17-C15;A6-B17-C16; A6-B17-C17; A6-B17-C18; A6-B17-C19; A6-B17-C20; A6-B17-C21;A6-B17-C22; A6-B17-C23; A6-B17-C24; A6-B17-C25; A6-B17-C26; A6-B17-C27;A6-B17-C28; A6-B17-C29; A6-B17-C30; A6-B17-C31; A6-B17-C32; A6-B17-C33;A6-B17-C34; A6-B17-C35; A6-B17-C36; A6-B17-C37; A6-B17-C38; A6-B17-C39;A6-B17-C40; A6-B17-C41; A6-B17-C42; A6-B17-C43; A6-B17-C44; A6-B17-C45;A6-B17-C46; A7-B17-C1; A7-B17-C2; A7-B17-C3; A7-B17-C4; A7-B17-C5;A7-B17-C6; A7-B17-C7; A7-B17-C8; A7-B17-C9; A7-B17-C10; A7-B17-C11;A7-B17-C12; A7-B17-C13; A7-B17-C14; A7-B17-C15; A7-B17-C16; A7-B17-C17;A7-B17-C18; A7-B17-C19; A7-B17-C20; A7-B17-C21; A7-B17-C22; A7-B17-C23;A7-B17-C24; A7-B17-C25; A7-B17-C26; A7-B17-C27; A7-B17-C28; A7-B17-C29;A7-B17-C30; A7-B17-C31; A7-B17-C32; A7-B17-C33; A7-B17-C34; A7-B17-C35;A7-B17-C36; A7-B17-C37; A7-B17-C38; A7-B17-C39; A7-B17-C40; A7-B17-C41;A7-B17-C42; A7-B17-C43; A7-B17-C44; A7-B17-C45; A7-B17-C46; A8-B17-C1;A8-B17-C2; A8-B17-C3; A8-B17-C4; A8-B17-C5; A8-B17-C6; A8-B17-C7;A8-B17-C8; A8-B17-C9; A8-B17-C10; A8-B17-C11; A8-B17-C12; A8-B17-C13;A8-B17-C14; A8-B17-C15; A8-B17-C16; A8-B17-C17; A8-B17-C18; A8-B17-C19;A8-B17-C20; A8-B17-C21; A8-B17-C22; A8-B17-C23; A8-B17-C24; A8-B17-C25;A8-B17-C26; A8-B17-C27; A8-B17-C28; A8-B17-C29; A8-B17-C30; A8-B17-C31;A8-B17-C32; A8-B17-C33; A8-B17-C34; A8-B17-C35; A8-B17-C36; A8-B17-C37;A8-B17-C38; A8-B17-C39; A8-B17-C40; A8-B17-C41; A8-B17-C42; A8-B17-C43;A8-B17-C44; A8-B17-C45; A8-B17-C46; A9-B17-C1; A9-B17-C2; A9-B17-C3;A9-B17-C4; A9-B17-C5; A9-B17-C6; A9-B17-C7; A9-B17-C8; A9-B17-C9;A9-B17-C10; A9-B17-C11; A9-B17-C12; A9-B17-C13; A9-B17-C14; A9-B17-C15;A9-B17-C16; A9-B17-C17; A9-B17-C18; A9-B17-C19; A9-B17-C20; A9-B17-C21;A9-B17-C22; A9-B17-C23; A9-B17-C24; A9-B17-C25; A9-B17-C26; A9-B17-C27;A9-B17-C28; A9-B17-C29; A9-B17-C30; A9-B17-C31; A9-B17-C32; A9-B17-C33;A9-B17-C34; A9-B17-C35; A9-B17-C36; A9-B17-C37; A9-B17-C38; A9-B17-C39;A9-B17-C40; A9-B17-C41; A9-B17-C42; A9-B17-C43; A9-B17-C44; A9-B17-C45;A9-B17-C46; A10-B17-C1; A10-B17-C2; A10-B17-C3; A10-B17-C4; A10-B17-C5;A10-B17-C6; A10-B17-C7; A10-B17-C8; A10-B17-C9; A10-B17-C10;A10-B17-C11; A10-B17-C12; A10-B17-C13; A10-B17-C14; A10-B17-C15;A10-B17-C16; A10-B17-C17; A10-B17-C18; A10-B17-C19; A10-B17-C20;A10-B17-C21; A10-B17-C22; A10-B17-C23; A10-B17-C24; A10-B17-C25;A10-B17-C26; A10-B17-C27; A10-B17-C28; A10-B17-C29; A10-B17-C30;A10-B17-C31; A10-B17-C32; A10-B17-C33; A10-B17-C34; A10-B17-C35;A10-B17-C36; A10-B17-C37; A10-B17-C38; A10-B17-C39; A10-B17-C40;A10-B17-C41; A10-B17-C42; A10-B17-C43; A10-B17-C44; A10-B17-C45;A10-B17-C46; A11-B17-C1; A11-B17-C2; A11-B17-C3; A11-B17-C4; A11-B17-C5;A11-B17-C6; A11-B17-C7; A11-B17-C8; A11-B17-C9; A11-B17-C10;A11-B17-C11; A11-B17-C12; A11-B17-C13; A11-B17-C14; A11-B17-C15;A11-B17-C16; A11-B17-C17; A11-B17-C18; A11-B17-C19; A11-B17-C20;A11-B17-C21; A11-B17-C22; A11-B17-C23; A11-B17-C24; A11-B17-C25;A11-B17-C26; A11-B17-C27; A11-B17-C28; A11-B17-C29; A11-B17-C30;A11-B17-C31; A11-B17-C32; A11-B17-C33; A11-B17-C34; A11-B17-C35;A11-B17-C36; A11-B17-C37; A11-B17-C38; A11-B17-C39; A11-B17-C40;A11-B17-C41; A11-B17-C42; A11-B17-C43; A11-B17-C44; A11-B17-C45;A11-B17-C46; A12-B17-C1; A12-B17-C2; A12-B17-C3; A12-B17-C4; A12-B17-C5;A12-B17-C6; A12-B17-C7; A12-B17-C8; A12-B17-C9; A12-B17-C10;A12-B17-C11; A12-B17-C12; A12-B17-C13; A12-B17-C14; A12-B17-C15;A12-B17-C16; A12-B17-C17; A12-B17-C18; A12-B17-C19; A12-B17-C20;A12-B17-C21; A12-B17-C22; A12-B17-C23; A12-B17-C24; A12-B17-C25;A12-B17-C26; A12-B17-C27; A12-B17-C28; A12-B17-C29; A12-B17-C30;A12-B17-C31; A12-B17-C32; A12-B17-C33; A12-B17-C34; A12-B17-C35;A12-B17-C36; A12-B17-C37; A12-B17-C38; A12-B17-C39; A12-B17-C40;A12-B17-C41; A12-B17-C42; A12-B17-C43; A12-B17-C44; A12-B17-C45;A12-B17-C46; A13-B17-C1; A13-B17-C2; A13-B17-C3; A13-B17-C4; A13-B17-C5;A13-B17-C6; A13-B17-C7; A13-B17-C8; A13-B17-C9; A13-B17-C10;A13-B17-C11; A13-B17-C12; A13-B17-C13; A13-B17-C14; A13-B17-C15;A13-B17-C16; A13-B17-C17; A13-B17-C18; A13-B17-C19; A13-B17-C20;A13-B17-C21; A13-B17-C22; A13-B17-C23; A13-B17-C24; A13-B17-C25;A13-B17-C26; A13-B17-C27; A13-B17-C28; A13-B17-C29; A13-B17-C30;A13-B17-C31; A13-B17-C32; A13-B17-C33; A13-B17-C34; A13-B17-C35;A13-B17-C36; A13-B17-C37; A13-B17-C38; A13-B17-C39; A13-B17-C40;A13-B17-C41; A13-B17-C42; A13-B17-C43; A13-B17-C44; A13-B17-C45;A13-B17-C46; A14-B17-C1; A14-B17-C2; A14-B17-C3; A14-B17-C4; A14-B17-C5;A14-B17-C6; A14-B17-C7; A14-B17-C8; A14-B17-C9; A14-B17-C10;A14-B17-C11; A14-B17-C12; A14-B17-C13; A14-B17-C14; A14-B17-C15;A14-B17-C16; A14-B17-C17; A14-B17-C18; A14-B17-C19; A14-B17-C20;A14-B17-C21; A14-B17-C22; A14-B17-C23; A14-B17-C24; A14-B17-C25;A14-B17-C26; A14-B17-C27; A14-B17-C28; A14-B17-C29; A14-B17-C30;A14-B17-C31; A14-B17-C32; A14-B17-C33; A14-B17-C34; A14-B17-C35;A14-B17-C36; A14-B17-C37; A14-B17-C38; A14-B17-C39; A14-B17-C40;A14-B17-C41; A14-B17-C42; A14-B17-C43; A14-B17-C44; A14-B17-C45;A14-B17-C46; A15-B17-C1; A15-B17-C2; A15-B17-C3; A15-B17-C4; A15-B17-C5;A15-B17-C6; A15-B17-C7; A15-B17-C8; A15-B17-C9; A15-B17-C10;A15-B17-C11; A15-B17-C12; A15-B17-C13; A15-B17-C14; A15-B17-C15;A15-B17-C16; A15-B17-C17; A15-B17-C18; A15-B17-C19; A15-B17-C20;A15-B17-C21; A15-B17-C22; A15-B17-C23; A15-B17-C24; A15-B17-C25;A15-B17-C26; A15-B17-C27; A15-B17-C28; A15-B17-C29; A15-B17-C30;A15-B17-C31; A15-B17-C32; A15-B17-C33; A15-B17-C34; A15-B17-C35;A15-B17-C36; A15-B17-C37; A15-B17-C38; A15-B17-C39; A15-B17-C40;A15-B17-C41; A15-B17-C42; A15-B17-C43; A15-B17-C44; A15-B17-C45;A15-B17-C46; A16-B17-C1; A16-B17-C2; A16-B17-C3; A16-B17-C4; A16-B17-C5;A16-B17-C6; A16-B17-C7; A16-B17-C8; A16-B17-C9; A16-B17-C10;A16-B17-C11; A16-B17-C12; A16-B17-C13; A16-B17-C14; A16-B17-C15;A16-B17-C16; A16-B17-C17; A16-B17-C18; A16-B17-C19; A16-B17-C20;A16-B17-C21; A16-B17-C22; A16-B17-C23; A16-B17-C24; A16-B17-C25;A16-B17-C26; A16-B17-C27; A16-B17-C28; A16-B17-C29; A16-B17-C30;A16-B17-C31; A16-B17-C32; A16-B17-C33; A16-B17-C34; A16-B17-C35;A16-B17-C36; A16-B17-C37; A16-B17-C38; A16-B17-C39; A16-B17-C40;A16-B17-C41; A16-B17-C42; A16-B17-C43; A16-B17-C44; A16-B17-C45;A16-B17-C46; A17-B17-C1; A17-B17-C2; A17-B17-C3; A17-B17-C4; A17-B17-C5;A17-B17-C6; A17-B17-C7; A17-B17-C8; A17-B17-C9; A17-B17-C10;A17-B17-C11; A17-B17-C12; A17-B17-C13; A17-B17-C14; A17-B17-C15;A17-B17-C16; A17-B17-C17; A17-B17-C18; A17-B17-C19; A17-B17-C20;A17-B17-C21; A17-B17-C22; A17-B17-C23; A17-B17-C24; A17-B17-C25;A17-B17-C26; A17-B17-C27; A17-B17-C28; A17-B17-C29; A17-B17-C30;A17-B17-C31; A17-B17-C32; A17-B17-C33; A17-B17-C34; A17-B17-C35;A17-B17-C36; A17-B17-C37; A17-B17-C38; A17-B17-C39; A17-B17-C40;A17-B17-C41; A17-B17-C42; A17-B17-C43; A17-B17-C44; A17-B17-C45;A17-B17-C46; A18-B17-C1; A18-B17-C2; A18-B17-C3; A18-B17-C4; A18-B17-C5;A18-B17-C6; A18-B17-C7; A18-B17-C8; A18-B17-C9; A18-B17-C10;A18-B17-C11; A18-B17-C12; A18-B17-C13; A18-B17-C14; A18-B17-C15;A18-B17-C16; A18-B17-C17; A18-B17-C18; A18-B17-C19; A18-B17-C20;A18-B17-C21; A18-B17-C22; A18-B17-C23; A18-B17-C24; A18-B17-C25;A18-B17-C26; A18-B17-C27; A18-B17-C28; A18-B17-C29; A18-B17-C30;A18-B17-C31; A18-B17-C32; A18-B17-C33; A18-B17-C34; A18-B17-C35;A18-B17-C36; A18-B17-C37; A18-B17-C38; A18-B17-C39; A18-B17-C40;A18-B17-C41; A18-B17-C42; A18-B17-C43; A18-B17-C44; A18-B17-C45;A18-B17-C46; A19-B17-C1; A19-B17-C2; A19-B17-C3; A19-B17-C4; A19-B17-C5;A19-B17-C6; A19-B17-C7; A19-B17-C8; A19-B17-C9; A19-B17-C10;A19-B17-C11; A19-B17-C12; A19-B17-C13; A19-B17-C14; A19-B17-C15;A19-B17-C16; A19-B17-C17; A19-B17-C18; A19-B17-C19; A19-B17-C20;A19-B17-C21; A19-B17-C22; A19-B17-C23; A19-B17-C24; A19-B17-C25;A19-B17-C26; A19-B17-C27; A19-B17-C28; A19-B17-C29; A19-B17-C30;A19-B17-C31; A19-B17-C32; A19-B17-C33; A19-B17-C34; A19-B17-C35;A19-B17-C36; A19-B17-C37; A19-B17-C38; A19-B17-C39; A19-B17-C40;A19-B17-C41; A19-B17-C42; A19-B17-C43; A19-B17-C44; A19-B17-C45;A19-B17-C46; A20-B17-C1; A20-B17-C2; A20-B17-C3; A20-B17-C4; A20-B17-C5;A20-B17-C6; A20-B17-C7; A20-B17-C8; A20-B17-C9; A20-B17-C10;A20-B17-C11; A20-B17-C12; A20-B17-C13; A20-B17-C14; A20-B17-C15;A20-B17-C16; A20-B17-C17; A20-B17-C18; A20-B17-C19; A20-B17-C20;A20-B17-C21; A20-B17-C22; A20-B17-C23; A20-B17-C24; A20-B17-C25;A20-B17-C26; A20-B17-C27; A20-B17-C28; A20-B17-C29; A20-B17-C30;A20-B17-C31; A20-B17-C32; A20-B17-C33; A20-B17-C34; A20-B17-C35;A20-B17-C36; A20-B17-C37; A20-B17-C38; A20-B17-C39; A20-B17-C40;A20-B17-C41; A20-B17-C42; A20-B17-C43; A20-B17-C44; A20-B17-C45;A20-B17-C46; A21-B17-C1; A21-B17-C2; A21-B17-C3; A21-B17-C4; A21-B17-C5;A21-B17-C6; A21-B17-C7; A21-B17-C8; A21-B17-C9; A21-B17-C10;A21-B17-C11; A21-B17-C12; A21-B17-C13; A21-B17-C14; A21-B17-C15;A21-B17-C16; A21-B17-C17; A21-B17-C18; A21-B17-C19; A21-B17-C20;A21-B17-C21; A21-B17-C22; A21-B17-C23; A21-B17-C24; A21-B17-C25;A21-B17-C26; A21-B17-C27; A21-B17-C28; A21-B17-C29; A21-B17-C30;A21-B17-C31; A21-B17-C32; A21-B17-C33; A21-B17-C34; A21-B17-C35;A21-B17-C36; A21-B17-C37; A21-B17-C38; A21-B17-C39; A21-B17-C40;A21-B17-C41; A21-B17-C42; A21-B17-C43; A21-B17-C44; A21-B17-C45;A21-B17-C46; A22-B17-C1; A22-B17-C2; A22-B17-C3; A22-B17-C4; A22-B17-C5;A22-B17-C6; A22-B17-C7; A22-B17-C8; A22-B17-C9; A22-B17-C10;A22-B17-C11; A22-B17-C12; A22-B17-C13; A22-B17-C14; A22-B17-C15;A22-B17-C16; A22-B17-C17; A22-B17-C18; A22-B17-C19; A22-B17-C20;A22-B17-C21; A22-B17-C22; A22-B17-C23; A22-B17-C24; A22-B17-C25;A22-B17-C26; A22-B17-C27; A22-B17-C28; A22-B17-C29; A22-B17-C30;A22-B17-C31; A22-B17-C32; A22-B17-C33; A22-B17-C34; A22-B17-C35;A22-B17-C36; A22-B17-C37; A22-B17-C38; A22-B17-C39; A22-B17-C40;A22-B17-C41; A22-B17-C42; A22-B17-C43; A22-B17-C44; A22-B17-C45;A22-B17-C46; A23-B17-C1; A23-B17-C2; A23-B17-C3; A23-B17-C4; A23-B17-C5;A23-B17-C6; A23-B17-C7; A23-B17-C8; A23-B17-C9; A23-B17-C10;A23-B17-C11; A23-B17-C12; A23-B17-C13; A23-B17-C14; A23-B17-C15;A23-B17-C16; A23-B17-C17; A23-B17-C18; A23-B17-C19; A23-B17-C20;A23-B17-C21; A23-B17-C22; A23-B17-C23; A23-B17-C24; A23-B17-C25;A23-B17-C26; A23-B17-C27; A23-B17-C28; A23-B17-C29; A23-B17-C30;A23-B17-C31; A23-B17-C32; A23-B17-C33; A23-B17-C34; A23-B17-C35;A23-B17-C36; A23-B17-C37; A23-B17-C38; A23-B17-C39; A23-B17-C40;A23-B17-C41; A23-B17-C42; A23-B17-C43; A23-B17-C44; A23-B17-C45;A23-B17-C46; A24-B17-C1; A24-B17-C2; A24-B17-C3; A24-B17-C4; A24-B17-C5;A24-B17-C6; A24-B17-C7; A24-B17-C8; A24-B17-C9; A24-B17-C10;A24-B17-C11; A24-B17-C12; A24-B17-C13; A24-B17-C14; A24-B17-C15;A24-B17-C16; A24-B17-C17; A24-B17-C18; A24-B17-C19; A24-B17-C20;A24-B17-C21; A24-B17-C22; A24-B17-C23; A24-B17-C24; A24-B17-C25;A24-B17-C26; A24-B17-C27; A24-B17-C28; A24-B17-C29; A24-B17-C30;A24-B17-C31; A24-B17-C32; A24-B17-C33; A24-B17-C34; A24-B17-C35;A24-B17-C36; A24-B17-C37; A24-B17-C38; A24-B17-C39; A24-B17-C40;A24-B17-C41; A24-B17-C42; A24-B17-C43; A24-B17-C44; A24-B17-C45;A24-B17-C46; A25-B17-C1; A25-B17-C2; A25-B17-C3; A25-B17-C4; A25-B17-C5;A25-B17-C6; A25-B17-C7; A25-B17-C8; A25-B17-C9; A25-B17-C10;A25-B17-C11; A25-B17-C12; A25-B17-C13; A25-B17-C14; A25-B17-C15;A25-B17-C16; A25-B17-C17; A25-B17-C18; A25-B17-C19; A25-B17-C20;A25-B17-C21; A25-B17-C22; A25-B17-C23; A25-B17-C24; A25-B17-C25;A25-B17-C26; A25-B17-C27; A25-B17-C28; A25-B17-C29; A25-B17-C30;A25-B17-C31; A25-B17-C32; A25-B17-C33; A25-B17-C34; A25-B17-C35;A25-B17-C36; A25-B17-C37; A25-B17-C38; A25-B17-C39; A25-B17-C40;A25-B17-C41; A25-B17-C42; A25-B17-C43; A25-B17-C44; A25-B17-C45;A25-B17-C46; A26-B17-C1; A26-B17-C2; A26-B17-C3; A26-B17-C4; A26-B17-C5;A26-B17-C6; A26-B17-C7; A26-B17-C8; A26-B17-C9; A26-B17-C10;A26-B17-C11; A26-B17-C12; A26-B17-C13; A26-B17-C14; A26-B17-C15;A26-B17-C16; A26-B17-C17; A26-B17-C18; A26-B17-C19; A26-B17-C20;A26-B17-C21; A26-B17-C22; A26-B17-C23; A26-B17-C24; A26-B17-C25;A26-B17-C26; A26-B17-C27; A26-B17-C28; A26-B17-C29; A26-B17-C30;A26-B17-C31; A26-B17-C32; A26-B17-C33; A26-B17-C34; A26-B17-C35;A26-B17-C36; A26-B17-C37; A26-B17-C38; A26-B17-C39; A26-B17-C40;A26-B17-C41; A26-B17-C42; A26-B17-C43; A26-B17-C44; A26-B17-C45;A26-B17-C46; A27-B17-C1; A27-B17-C2; A27-B17-C3; A27-B17-C4; A27-B17-C5;A27-B17-C6; A27-B17-C7; A27-B17-C8; A27-B17-C9; A27-B17-C10;A27-B17-C11; A27-B17-C12; A27-B17-C13; A27-B17-C14; A27-B17-C15;A27-B17-C16; A27-B17-C17; A27-B17-C18; A27-B17-C19; A27-B17-C20;A27-B17-C21; A27-B17-C22; A27-B17-C23; A27-B17-C24; A27-B17-C25;A27-B17-C26; A27-B17-C27; A27-B17-C28; A27-B17-C29; A27-B17-C30;A27-B17-C31; A27-B17-C32; A27-B17-C33; A27-B17-C34; A27-B17-C35;A27-B17-C36; A27-B17-C37; A27-B17-C38; A27-B17-C39; A27-B17-C40;A27-B17-C41; A27-B17-C42; A27-B17-C43; A27-B17-C44; A27-B17-C45;A27-B17-C46; A28-B17-C1; A28-B17-C2; A28-B17-C3; A28-B17-C4; A28-B17-C5;A28-B17-C6; A28-B17-C7; A28-B17-C8; A28-B17-C9; A28-B17-C10;A28-B17-C11; A28-B17-C12; A28-B17-C13; A28-B17-C14; A28-B17-C15;A28-B17-C16; A28-B17-C17; A28-B17-C18; A28-B17-C19; A28-B17-C20;A28-B17-C21; A28-B17-C22; A28-B17-C23; A28-B17-C24; A28-B17-C25;A28-B17-C26; A28-B17-C27; A28-B17-C28; A28-B17-C29; A28-B17-C30;A28-B17-C31; A28-B17-C32; A28-B17-C33; A28-B17-C34; A28-B17-C35;A28-B17-C36; A28-B17-C37; A28-B17-C38; A28-B17-C39; A28-B17-C40;A28-B17-C41; A28-B17-C42; A28-B17-C43; A28-B17-C44; A28-B17-C45;A28-B17-C46; A1-B18-C1; A1-B18-C2; A1-B18-C3; A1-B18-C4; A1-B18-C5;A1-B18-C6; A1-B18-C7; A1-B18-C8; A1-B18-C9; A1-B18-C10; A1-B18-C11;A1-B18-C12; A1-B18-C13; A1-B18-C14; A1-B18-C15; A1-B18-C16; A1-B18-C17;A1-B18-C18; A1-B18-C19; A1-B18-C20; A1-B18-C21; A1-B18-C22; A1-B18-C23;A1-B18-C24; A1-B18-C25; A1-B18-C26; A1-B18-C27; A1-B18-C28; A1-B18-C29;A1-B18-C30; A1-B18-C31; A1-B18-C32; A1-B18-C33; A1-B18-C34; A1-B18-C35;A1-B18-C36; A1-B18-C37; A1-B18-C38; A1-B18-C39; A1-B18-C40; A1-B18-C41;A1-B18-C42; A1-B18-C43; A1-B18-C44; A1-B18-C45; A1-B18-C46; A2-B18-C1;A2-B18-C2; A2-B18-C3; A2-B18-C4; A2-B18-C5; A2-B18-C6; A2-B18-C7;A2-B18-C8; A2-B18-C9; A2-B18-C10; A2-B18-C11; A2-B18-C12; A2-B18-C13;A2-B18-C14; A2-B18-C15; A2-B18-C16; A2-B18-C17; A2-B18-C18; A2-B18-C19;A2-B18-C20; A2-B18-C21; A2-B18-C22; A2-B18-C23; A2-B18-C24; A2-B18-C25;A2-B18-C26; A2-B18-C27; A2-B18-C28; A2-B18-C29; A2-B18-C30; A2-B18-C31;A2-B18-C32; A2-B18-C33; A2-B18-C34; A2-B18-C35; A2-B18-C36; A2-B18-C37;A2-B18-C38; A2-B18-C39; A2-B18-C40; A2-B18-C41; A2-B18-C42; A2-B18-C43;A2-B18-C44; A2-B18-C45; A2-B18-C46; A3-B18-C1; A3-B18-C2; A3-B18-C3;A3-B18-C4; A3-B18-C5; A3-B18-C6; A3-B18-C7; A3-B18-C8; A3-B18-C9;A3-B18-C10; A3-B18-C11; A3-B18-C12; A3-B18-C13; A3-B18-C14; A3-B18-C15;A3-B18-C16; A3-B18-C17; A3-B18-C18; A3-B18-C19; A3-B18-C20; A3-B18-C21;A3-B18-C22; A3-B18-C23; A3-B18-C24; A3-B18-C25; A3-B18-C26; A3-B18-C27;A3-B18-C28; A3-B18-C29; A3-B18-C30; A3-B18-C31; A3-B18-C32; A3-B18-C33;A3-B18-C34; A3-B18-C35; A3-B18-C36; A3-B18-C37; A3-B18-C38; A3-B18-C39;A3-B18-C40; A3-B18-C41; A3-B18-C42; A3-B18-C43; A3-B18-C44; A3-B18-C45;A3-B18-C46; A4-B18-C1; A4-B18-C2; A4-B18-C3; A4-B18-C4; A4-B18-C5;A4-B18-C6; A4-B18-C7; A4-B18-C8; A4-B18-C9; A4-B18-C10; A4-B18-C11;A4-B18-C12; A4-B18-C13; A4-B18-C14; A4-B18-C15; A4-B18-C16; 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A6-B18-C12; A6-B18-C13; A6-B18-C14; A6-B18-C15;A6-B18-C16; A6-B18-C17; A6-B18-C18; A6-B18-C19; A6-B18-C20; A6-B18-C21;A6-B18-C22; A6-B18-C23; A6-B18-C24; A6-B18-C25; A6-B18-C26; A6-B18-C27;A6-B18-C28; A6-B18-C29; A6-B18-C30; A6-B18-C31; A6-B18-C32; A6-B18-C33;A6-B18-C34; A6-B18-C35; A6-B18-C36; A6-B18-C37; A6-B18-C38; A6-B18-C39;A6-B18-C40; A6-B18-C41; A6-B18-C42; A6-B18-C43; A6-B18-C44; A6-B18-C45;A6-B18-C46; A7-B18-C1; A7-B18-C2; A7-B18-C3; A7-B18-C4; A7-B18-C5;A7-B18-C6; A7-B18-C7; A7-B18-C8; A7-B18-C9; A7-B18-C10; A7-B18-C11;A7-B18-C12; A7-B18-C13; A7-B18-C14; A7-B18-C15; A7-B18-C16; A7-B18-C17;A7-B18-C18; A7-B18-C19; A7-B18-C20; A7-B18-C21; A7-B18-C22; A7-B18-C23;A7-B18-C24; A7-B18-C25; A7-B18-C26; A7-B18-C27; A7-B18-C28; A7-B18-C29;A7-B18-C30; A7-B18-C31; A7-B18-C32; A7-B18-C33; A7-B18-C34; A7-B18-C35;A7-B18-C36; A7-B18-C37; A7-B18-C38; A7-B18-C39; A7-B18-C40; A7-B18-C41;A7-B18-C42; A7-B18-C43; A7-B18-C44; A7-B18-C45; A7-B18-C46; A8-B18-C1;A8-B18-C2; A8-B18-C3; A8-B18-C4; A8-B18-C5; A8-B18-C6; A8-B18-C7;A8-B18-C8; A8-B18-C9; A8-B18-C10; A8-B18-C11; A8-B18-C12; A8-B18-C13;A8-B18-C14; A8-B18-C15; A8-B18-C16; A8-B18-C17; A8-B18-C18; A8-B18-C19;A8-B18-C20; A8-B18-C21; A8-B18-C22; A8-B18-C23; A8-B18-C24; A8-B18-C25;A8-B18-C26; A8-B18-C27; A8-B18-C28; A8-B18-C29; A8-B18-C30; A8-B18-C31;A8-B18-C32; A8-B18-C33; A8-B18-C34; A8-B18-C35; A8-B18-C36; A8-B18-C37;A8-B18-C38; A8-B18-C39; A8-B18-C40; A8-B18-C41; A8-B18-C42; A8-B18-C43;A8-B18-C44; A8-B18-C45; A8-B18-C46; A9-B18-C1; A9-B18-C2; A9-B18-C3;A9-B18-C4; A9-B18-C5; A9-B18-C6; A9-B18-C7; A9-B18-C8; A9-B18-C9;A9-B18-C10; A9-B18-C11; A9-B18-C12; A9-B18-C13; A9-B18-C14; A9-B18-C15;A9-B18-C16; A9-B18-C17; A9-B18-C18; A9-B18-C19; A9-B18-C20; A9-B18-C21;A9-B18-C22; A9-B18-C23; A9-B18-C24; A9-B18-C25; A9-B18-C26; A9-B18-C27;A9-B18-C28; A9-B18-C29; A9-B18-C30; A9-B18-C31; A9-B18-C32; A9-B18-C33;A9-B18-C34; A9-B18-C35; A9-B18-C36; A9-B18-C37; A9-B18-C38; A9-B18-C39;A9-B18-C40; A9-B18-C41; A9-B18-C42; A9-B18-C43; A9-B18-C44; A9-B18-C45;A9-B18-C46; A10-B18-C1; A10-B18-C2; A10-B18-C3; A10-B18-C4; A10-B18-C5;A10-B18-C6; A10-B18-C7; A10-B18-C8; A10-B18-C9; A10-B18-C10;A10-B18-C11; A10-B18-C12; A10-B18-C13; A10-B18-C14; A10-B18-C15;A10-B18-C16; A10-B18-C17; A10-B18-C18; A10-B18-C19; A10-B18-C20;A10-B18-C21; A10-B18-C22; A10-B18-C23; A10-B18-C24; A10-B18-C25;A10-B18-C26; A10-B18-C27; A10-B18-C28; A10-B18-C29; A10-B18-C30;A10-B18-C31; A10-B18-C32; A10-B18-C33; A10-B18-C34; A10-B18-C35;A10-B18-C36; A10-B18-C37; A10-B18-C38; A10-B18-C39; A10-B18-C40;A10-B18-C41; A10-B18-C42; A10-B18-C43; A10-B18-C44; A10-B18-C45;A10-B18-C46; A11-B18-C1; A11-B18-C2; A11-B18-C3; A11-B18-C4; A11-B18-C5;A11-B18-C6; A11-B18-C7; A11-B18-C8; A11-B18-C9; A11-B18-C10;A11-B18-C11; A11-B18-C12; A11-B18-C13; A11-B18-C14; A11-B18-C15;A11-B18-C16; A11-B18-C17; A11-B18-C18; A11-B18-C19; A11-B18-C20;A11-B18-C21; A11-B18-C22; A11-B18-C23; A11-B18-C24; A11-B18-C25;A11-B18-C26; A11-B18-C27; A11-B18-C28; A11-B18-C29; A11-B18-C30;A11-B18-C31; A11-B18-C32; A11-B18-C33; A11-B18-C34; 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A13-B18-C23; A13-B18-C24; A13-B18-C25;A13-B18-C26; A13-B18-C27; A13-B18-C28; A13-B18-C29; A13-B18-C30;A13-B18-C31; A13-B18-C32; A13-B18-C33; A13-B18-C34; A13-B18-C35;A13-B18-C36; A13-B18-C37; A13-B18-C38; A13-B18-C39; A13-B18-C40;A13-B18-C41; A13-B18-C42; A13-B18-C43; A13-B18-C44; A13-B18-C45;A13-B18-C46; A14-B18-C1; A14-B18-C2; A14-B18-C3; A14-B18-C4; A14-B18-C5;A14-B18-C6; A14-B18-C7; A14-B18-C8; A14-B18-C9; A14-B18-C10;A14-B18-C11; A14-B18-C12; A14-B18-C13; A14-B18-C14; A14-B18-C15;A14-B18-C16; A14-B18-C17; A14-B18-C18; A14-B18-C19; A14-B18-C20;A14-B18-C21; A14-B18-C22; A14-B18-C23; A14-B18-C24; A14-B18-C25;A14-B18-C26; A14-B18-C27; A14-B18-C28; A14-B18-C29; A14-B18-C30;A14-B18-C31; A14-B18-C32; A14-B18-C33; A14-B18-C34; A14-B18-C35;A14-B18-C36; A14-B18-C37; A14-B18-C38; A14-B18-C39; A14-B18-C40;A14-B18-C41; A14-B18-C42; A14-B18-C43; A14-B18-C44; A14-B18-C45;A14-B18-C46; A15-B18-C1; A15-B18-C2; A15-B18-C3; A15-B18-C4; A15-B18-C5;A15-B18-C6; A15-B18-C7; A15-B18-C8; A15-B18-C9; A15-B18-C10;A15-B18-C11; A15-B18-C12; A15-B18-C13; A15-B18-C14; A15-B18-C15;A15-B18-C16; A15-B18-C17; A15-B18-C18; A15-B18-C19; A15-B18-C20;A15-B18-C21; A15-B18-C22; A15-B18-C23; A15-B18-C24; A15-B18-C25;A15-B18-C26; A15-B18-C27; A15-B18-C28; A15-B18-C29; A15-B18-C30;A15-B18-C31; A15-B18-C32; A15-B18-C33; A15-B18-C34; A15-B18-C35;A15-B18-C36; A15-B18-C37; A15-B18-C38; A15-B18-C39; A15-B18-C40;A15-B18-C41; A15-B18-C42; A15-B18-C43; A15-B18-C44; A15-B18-C45;A15-B18-C46; A16-B18-C1; A16-B18-C2; A16-B18-C3; A16-B18-C4; A16-B18-C5;A16-B18-C6; A16-B18-C7; A16-B18-C8; A16-B18-C9; A16-B18-C10;A16-B18-C11; A16-B18-C12; A16-B18-C13; A16-B18-C14; A16-B18-C15;A16-B18-C16; A16-B18-C17; A16-B18-C18; A16-B18-C19; A16-B18-C20;A16-B18-C21; A16-B18-C22; A16-B18-C23; A16-B18-C24; A16-B18-C25;A16-B18-C26; A16-B18-C27; A16-B18-C28; A16-B18-C29; A16-B18-C30;A16-B18-C31; A16-B18-C32; A16-B18-C33; A16-B18-C34; A16-B18-C35;A16-B18-C36; A16-B18-C37; A16-B18-C38; A16-B18-C39; A16-B18-C40;A16-B18-C41; A16-B18-C42; A16-B18-C43; A16-B18-C44; A16-B18-C45;A16-B18-C46; A17-B18-C1; A17-B18-C2; A17-B18-C3; A17-B18-C4; A17-B18-C5;A17-B18-C6; A17-B18-C7; A17-B18-C8; A17-B18-C9; A17-B18-C10;A17-B18-C11; A17-B18-C12; A17-B18-C13; A17-B18-C14; A17-B18-C15;A17-B18-C16; A17-B18-C17; A17-B18-C18; A17-B18-C19; A17-B18-C20;A17-B18-C21; A17-B18-C22; A17-B18-C23; A17-B18-C24; A17-B18-C25;A17-B18-C26; A17-B18-C27; A17-B18-C28; A17-B18-C29; A17-B18-C30;A17-B18-C31; A17-B18-C32; A17-B18-C33; A17-B18-C34; A17-B18-C35;A17-B18-C36; A17-B18-C37; A17-B18-C38; A17-B18-C39; A17-B18-C40;A17-B18-C41; A17-B18-C42; A17-B18-C43; A17-B18-C44; A17-B18-C45;A17-B18-C46; A18-B18-C1; A18-B18-C2; A18-B18-C3; A18-B18-C4; A18-B18-C5;A18-B18-C6; A18-B18-C7; A18-B18-C8; A18-B18-C9; A18-B18-C10;A18-B18-C11; A18-B18-C12; A18-B18-C13; A18-B18-C14; A18-B18-C15;A18-B18-C16; A18-B18-C17; A18-B18-C18; A18-B18-C19; A18-B18-C20;A18-B18-C21; A18-B18-C22; A18-B18-C23; A18-B18-C24; A18-B18-C25;A18-B18-C26; A18-B18-C27; A18-B18-C28; A18-B18-C29; A18-B18-C30;A18-B18-C31; A18-B18-C32; A18-B18-C33; A18-B18-C34; A18-B18-C35;A18-B18-C36; A18-B18-C37; A18-B18-C38; A18-B18-C39; A18-B18-C40;A18-B18-C41; A18-B18-C42; A18-B18-C43; A18-B18-C44; A18-B18-C45;A18-B18-C46; A19-B18-C1; A19-B18-C2; A19-B18-C3; A19-B18-C4; A19-B18-C5;A19-B18-C6; A19-B18-C7; A19-B18-C8; A19-B18-C9; A19-B18-C10;A19-B18-C11; A19-B18-C12; A19-B18-C13; A19-B18-C14; A19-B18-C15;A19-B18-C16; A19-B18-C17; A19-B18-C18; A19-B18-C19; A19-B18-C20;A19-B18-C21; A19-B18-C22; A19-B18-C23; A19-B18-C24; A19-B18-C25;A19-B18-C26; A19-B18-C27; A19-B18-C28; A19-B18-C29; A19-B18-C30;A19-B18-C31; A19-B18-C32; A19-B18-C33; A19-B18-C34; A19-B18-C35;A19-B18-C36; A19-B18-C37; A19-B18-C38; A19-B18-C39; A19-B18-C40;A19-B18-C41; A19-B18-C42; A19-B18-C43; A19-B18-C44; A19-B18-C45;A19-B18-C46; A20-B18-C1; A20-B18-C2; A20-B18-C3; A20-B18-C4; A20-B18-C5;A20-B18-C6; A20-B18-C7; A20-B18-C8; A20-B18-C9; A20-B18-C10;A20-B18-C11; A20-B18-C12; A20-B18-C13; A20-B18-C14; A20-B18-C15;A20-B18-C16; A20-B18-C17; A20-B18-C18; A20-B18-C19; A20-B18-C20;A20-B18-C21; A20-B18-C22; A20-B18-C23; A20-B18-C24; A20-B18-C25;A20-B18-C26; A20-B18-C27; A20-B18-C28; A20-B18-C29; A20-B18-C30;A20-B18-C31; A20-B18-C32; A20-B18-C33; A20-B18-C34; A20-B18-C35;A20-B18-C36; A20-B18-C37; A20-B18-C38; A20-B18-C39; A20-B18-C40;A20-B18-C41; A20-B18-C42; A20-B18-C43; A20-B18-C44; A20-B18-C45;A20-B18-C46; A21-B18-C1; A21-B18-C2; A21-B18-C3; A21-B18-C4; A21-B18-C5;A21-B18-C6; A21-B18-C7; A21-B18-C8; A21-B18-C9; A21-B18-C10;A21-B18-C11; A21-B18-C12; A21-B18-C13; A21-B18-C14; A21-B18-C15;A21-B18-C16; A21-B18-C17; A21-B18-C18; A21-B18-C19; A21-B18-C20;A21-B18-C21; A21-B18-C22; A21-B18-C23; A21-B18-C24; A21-B18-C25;A21-B18-C26; A21-B18-C27; A21-B18-C28; A21-B18-C29; A21-B18-C30;A21-B18-C31; A21-B18-C32; A21-B18-C33; A21-B18-C34; A21-B18-C35;A21-B18-C36; A21-B18-C37; A21-B18-C38; A21-B18-C39; A21-B18-C40;A21-B18-C41; A21-B18-C42; A21-B18-C43; A21-B18-C44; A21-B18-C45;A21-B18-C46; A22-B18-C1; A22-B18-C2; A22-B18-C3; A22-B18-C4; A22-B18-C5;A22-B18-C6; A22-B18-C7; A22-B18-C8; A22-B18-C9; A22-B18-C10;A22-B18-C11; A22-B18-C12; A22-B18-C13; A22-B18-C14; A22-B18-C15;A22-B18-C16; A22-B18-C17; A22-B18-C18; A22-B18-C19; A22-B18-C20;A22-B18-C21; A22-B18-C22; A22-B18-C23; A22-B18-C24; A22-B18-C25;A22-B18-C26; A22-B18-C27; A22-B18-C28; A22-B18-C29; A22-B18-C30;A22-B18-C31; A22-B18-C32; A22-B18-C33; A22-B18-C34; A22-B18-C35;A22-B18-C36; A22-B18-C37; A22-B18-C38; A22-B18-C39; A22-B18-C40;A22-B18-C41; A22-B18-C42; A22-B18-C43; A22-B18-C44; A22-B18-C45;A22-B18-C46; A23-B18-C1; A23-B18-C2; A23-B18-C3; A23-B18-C4; A23-B18-C5;A23-B18-C6; A23-B18-C7; A23-B18-C8; A23-B18-C9; A23-B18-C10;A23-B18-C11; A23-B18-C12; A23-B18-C13; A23-B18-C14; A23-B18-C15;A23-B18-C16; A23-B18-C17; A23-B18-C18; A23-B18-C19; A23-B18-C20;A23-B18-C21; A23-B18-C22; A23-B18-C23; A23-B18-C24; A23-B18-C25;A23-B18-C26; A23-B18-C27; A23-B18-C28; A23-B18-C29; A23-B18-C30;A23-B18-C31; A23-B18-C32; A23-B18-C33; A23-B18-C34; A23-B18-C35;A23-B18-C36; A23-B18-C37; A23-B18-C38; A23-B18-C39; A23-B18-C40;A23-B18-C41; A23-B18-C42; A23-B18-C43; A23-B18-C44; A23-B18-C45;A23-B18-C46; A24-B18-C1; A24-B18-C2; A24-B18-C3; A24-B18-C4; A24-B18-C5;A24-B18-C6; A24-B18-C7; A24-B18-C8; A24-B18-C9; A24-B18-C10;A24-B18-C11; A24-B18-C12; A24-B18-C13; A24-B18-C14; A24-B18-C15;A24-B18-C16; A24-B18-C17; A24-B18-C18; A24-B18-C19; A24-B18-C20;A24-B18-C21; A24-B18-C22; A24-B18-C23; A24-B18-C24; A24-B18-C25;A24-B18-C26; A24-B18-C27; A24-B18-C28; A24-B18-C29; A24-B18-C30;A24-B18-C31; A24-B18-C32; A24-B18-C33; A24-B18-C34; A24-B18-C35;A24-B18-C36; A24-B18-C37; A24-B18-C38; A24-B18-C39; A24-B18-C40;A24-B18-C41; A24-B18-C42; A24-B18-C43; A24-B18-C44; A24-B18-C45;A24-B18-C46; A25-B18-C1; A25-B18-C2; A25-B18-C3; A25-B18-C4; A25-B18-C5;A25-B18-C6; A25-B18-C7; A25-B18-C8; A25-B18-C9; A25-B18-C10;A25-B18-C11; A25-B18-C12; A25-B18-C13; A25-B18-C14; A25-B18-C15;A25-B18-C16; A25-B18-C17; A25-B18-C18; A25-B18-C19; A25-B18-C20;A25-B18-C21; A25-B18-C22; A25-B18-C23; A25-B18-C24; A25-B18-C25;A25-B18-C26; A25-B18-C27; A25-B18-C28; A25-B18-C29; A25-B18-C30;A25-B18-C31; A25-B18-C32; A25-B18-C33; A25-B18-C34; A25-B18-C35;A25-B18-C36; A25-B18-C37; A25-B18-C38; A25-B18-C39; A25-B18-C40;A25-B18-C41; A25-B18-C42; A25-B18-C43; A25-B18-C44; A25-B18-C45;A25-B18-C46; A26-B18-C1; A26-B18-C2; A26-B18-C3; A26-B18-C4; A26-B18-C5;A26-B18-C6; A26-B18-C7; A26-B18-C8; A26-B18-C9; A26-B18-C10;A26-B18-C11; A26-B18-C12; A26-B18-C13; A26-B18-C14; A26-B18-C15;A26-B18-C16; A26-B18-C17; A26-B18-C18; A26-B18-C19; A26-B18-C20;A26-B18-C21; A26-B18-C22; A26-B18-C23; A26-B18-C24; A26-B18-C25;A26-B18-C26; A26-B18-C27; A26-B18-C28; A26-B18-C29; A26-B18-C30;A26-B18-C31; A26-B18-C32; A26-B18-C33; A26-B18-C34; A26-B18-C35;A26-B18-C36; A26-B18-C37; A26-B18-C38; A26-B18-C39; A26-B18-C40;A26-B18-C41; A26-B18-C42; A26-B18-C43; A26-B18-C44; A26-B18-C45;A26-B18-C46; A27-B18-C1; A27-B18-C2; A27-B18-C3; A27-B18-C4; A27-B18-C5;A27-B18-C6; A27-B18-C7; A27-B18-C8; A27-B18-C9; A27-B18-C10;A27-B18-C11; A27-B18-C12; A27-B18-C13; A27-B18-C14; A27-B18-C15;A27-B18-C16; A27-B18-C17; A27-B18-C18; A27-B18-C19; A27-B18-C20;A27-B18-C21; A27-B18-C22; A27-B18-C23; A27-B18-C24; A27-B18-C25;A27-B18-C26; A27-B18-C27; A27-B18-C28; A27-B18-C29; A27-B18-C30;A27-B18-C31; A27-B18-C32; A27-B18-C33; A27-B18-C34; A27-B18-C35;A27-B18-C36; A27-B18-C37; A27-B18-C38; A27-B18-C39; A27-B18-C40;A27-B18-C41; A27-B18-C42; A27-B18-C43; A27-B18-C44; A27-B18-C45;A27-B18-C46; A28-B18-C1; A28-B18-C2; A28-B18-C3; A28-B18-C4; A28-B18-C5;A28-B18-C6; A28-B18-C7; A28-B18-C8; A28-B18-C9; A28-B18-C10;A28-B18-C11; A28-B18-C12; A28-B18-C13; A28-B18-C14; A28-B18-C15;A28-B18-C16; A28-B18-C17; A28-B18-C18; A28-B18-C19; A28-B18-C20;A28-B18-C21; A28-B18-C22; A28-B18-C23; A28-B18-C24; A28-B18-C25;A28-B18-C26; A28-B18-C27; A28-B18-C28; A28-B18-C29; A28-B18-C30;A28-B18-C31; A28-B18-C32; A28-B18-C33; A28-B18-C34; A28-B18-C35;A28-B18-C36; A28-B18-C37; A28-B18-C38; A28-B18-C39; A28-B18-C40;A28-B18-C41; A28-B18-C42; A28-B18-C43; A28-B18-C44; A28-B18-C45;A28-B18-C46; A1-B19-C1; A1-B19-C2; A1-B19-C3; A1-B19-C4; A1-B19-C5;A1-B19-C6; A1-B19-C7; A1-B19-C8; A1-B19-C9; A1-B19-C10; A1-B19-C11;A1-B19-C12; A1-B19-C13; A1-B19-C14; A1-B19-C15; A1-B19-C16; A1-B19-C17;A1-B19-C18; A1-B19-C19; A1-B19-C20; A1-B19-C21; A1-B19-C22; A1-B19-C23;A1-B19-C24; A1-B19-C25; A1-B19-C26; A1-B19-C27; A1-B19-C28; A1-B19-C29;A1-B19-C30; A1-B19-C31; A1-B19-C32; A1-B19-C33; A1-B19-C34; A1-B19-C35;A1-B19-C36; A1-B19-C37; A1-B19-C38; A1-B19-C39; A1-B19-C40; A1-B19-C41;A1-B19-C42; A1-B19-C43; A1-B19-C44; A1-B19-C45; A1-B19-C46; A2-B19-C1;A2-B19-C2; A2-B19-C3; A2-B19-C4; A2-B19-C5; A2-B19-C6; A2-B19-C7;A2-B19-C8; A2-B19-C9; A2-B19-C10; A2-B19-C11; A2-B19-C12; A2-B19-C13;A2-B19-C14; A2-B19-C15; A2-B19-C16; A2-B19-C17; A2-B19-C18; A2-B19-C19;A2-B19-C20; A2-B19-C21; A2-B19-C22; A2-B19-C23; A2-B19-C24; A2-B19-C25;A2-B19-C26; A2-B19-C27; A2-B19-C28; A2-B19-C29; A2-B19-C30; A2-B19-C31;A2-B19-C32; A2-B19-C33; A2-B19-C34; A2-B19-C35; A2-B19-C36; A2-B19-C37;A2-B19-C38; A2-B19-C39; A2-B19-C40; A2-B19-C41; A2-B19-C42; A2-B19-C43;A2-B19-C44; A2-B19-C45; A2-B19-C46; A3-B19-C1; A3-B19-C2; A3-B19-C3;A3-B19-C4; A3-B19-C5; A3-B19-C6; A3-B19-C7; A3-B19-C8; A3-B19-C9;A3-B19-C10; A3-B19-C11; A3-B19-C12; A3-B19-C13; A3-B19-C14; A3-B19-C15;A3-B19-C16; A3-B19-C17; A3-B19-C18; A3-B19-C19; A3-B19-C20; A3-B19-C21;A3-B19-C22; A3-B19-C23; A3-B19-C24; A3-B19-C25; A3-B19-C26; A3-B19-C27;A3-B19-C28; A3-B19-C29; A3-B19-C30; A3-B19-C31; A3-B19-C32; A3-B19-C33;A3-B19-C34; A3-B19-C35; A3-B19-C36; A3-B19-C37; A3-B19-C38; A3-B19-C39;A3-B19-C40; A3-B19-C41; A3-B19-C42; A3-B19-C43; A3-B19-C44; A3-B19-C45;A3-B19-C46; A4-B19-C1; A4-B19-C2; A4-B19-C3; A4-B19-C4; A4-B19-C5;A4-B19-C6; A4-B19-C7; A4-B19-C8; A4-B19-C9; A4-B19-C10; A4-B19-C11;A4-B19-C12; A4-B19-C13; A4-B19-C14; A4-B19-C15; A4-B19-C16; A4-B19-C17;A4-B19-C18; A4-B19-C19; A4-B19-C20; A4-B19-C21; A4-B19-C22; A4-B19-C23;A4-B19-C24; A4-B19-C25; A4-B19-C26; A4-B19-C27; A4-B19-C28; A4-B19-C29;A4-B19-C30; A4-B19-C31; A4-B19-C32; A4-B19-C33; A4-B19-C34; A4-B19-C35;A4-B19-C36; A4-B19-C37; A4-B19-C38; A4-B19-C39; A4-B19-C40; A4-B19-C41;A4-B19-C42; A4-B19-C43; A4-B19-C44; A4-B19-C45; A4-B19-C46; A5-B19-C1;A5-B19-C2; A5-B19-C3; A5-B19-C4; A5-B19-C5; A5-B19-C6; A5-B19-C7;A5-B19-C8; A5-B19-C9; A5-B19-C10; A5-B19-C11; A5-B19-C12; A5-B19-C13;A5-B19-C14; A5-B19-C15; A5-B19-C16; A5-B19-C17; A5-B19-C18; A5-B19-C19;A5-B19-C20; A5-B19-C21; A5-B19-C22; A5-B19-C23; A5-B19-C24; A5-B19-C25;A5-B19-C26; A5-B19-C27; A5-B19-C28; A5-B19-C29; A5-B19-C30; A5-B19-C31;A5-B19-C32; A5-B19-C33; A5-B19-C34; A5-B19-C35; A5-B19-C36; A5-B19-C37;A5-B19-C38; A5-B19-C39; A5-B19-C40; A5-B19-C41; A5-B19-C42; A5-B19-C43;A5-B19-C44; A5-B19-C45; A5-B19-C46; A6-B19-C1; A6-B19-C2; A6-B19-C3;A6-B19-C4; A6-B19-C5; A6-B19-C6; A6-B19-C7; A6-B19-C8; A6-B19-C9;A6-B19-C10; A6-B19-C11; A6-B19-C12; A6-B19-C13; A6-B19-C14; A6-B19-C15;A6-B19-C16; A6-B19-C17; A6-B19-C18; A6-B19-C19; A6-B19-C20; A6-B19-C21;A6-B19-C22; A6-B19-C23; A6-B19-C24; A6-B19-C25; A6-B19-C26; A6-B19-C27;A6-B19-C28; A6-B19-C29; A6-B19-C30; A6-B19-C31; A6-B19-C32; A6-B19-C33;A6-B19-C34; A6-B19-C35; A6-B19-C36; A6-B19-C37; A6-B19-C38; A6-B19-C39;A6-B19-C40; A6-B19-C41; A6-B19-C42; A6-B19-C43; A6-B19-C44; A6-B19-C45;A6-B19-C46; A7-B19-C1; A7-B19-C2; A7-B19-C3; A7-B19-C4; A7-B19-C5;A7-B19-C6; A7-B19-C7; A7-B19-C8; A7-B19-C9; A7-B19-C10; A7-B19-C11;A7-B19-C12; A7-B19-C13; A7-B19-C14; A7-B19-C15; A7-B19-C16; A7-B19-C17;A7-B19-C18; A7-B19-C19; A7-B19-C20; A7-B19-C21; A7-B19-C22; A7-B19-C23;A7-B19-C24; A7-B19-C25; A7-B19-C26; A7-B19-C27; A7-B19-C28; A7-B19-C29;A7-B19-C30; A7-B19-C31; A7-B19-C32; A7-B19-C33; A7-B19-C34; A7-B19-C35;A7-B19-C36; A7-B19-C37; A7-B19-C38; A7-B19-C39; A7-B19-C40; A7-B19-C41;A7-B19-C42; A7-B19-C43; A7-B19-C44; A7-B19-C45; A7-B19-C46; A8-B19-C1;A8-B19-C2; A8-B19-C3; A8-B19-C4; A8-B19-C5; A8-B19-C6; A8-B19-C7;A8-B19-C8; A8-B19-C9; A8-B19-C10; A8-B19-C11; A8-B19-C12; A8-B19-C13;A8-B19-C14; A8-B19-C15; A8-B19-C16; A8-B19-C17; A8-B19-C18; A8-B19-C19;A8-B19-C20; A8-B19-C21; A8-B19-C22; A8-B19-C23; A8-B19-C24; A8-B19-C25;A8-B19-C26; A8-B19-C27; A8-B19-C28; A8-B19-C29; A8-B19-C30; A8-B19-C31;A8-B19-C32; A8-B19-C33; A8-B19-C34; A8-B19-C35; A8-B19-C36; A8-B19-C37;A8-B19-C38; A8-B19-C39; A8-B19-C40; A8-B19-C41; A8-B19-C42; A8-B19-C43;A8-B19-C44; A8-B19-C45; A8-B19-C46; A9-B19-C1; A9-B19-C2; A9-B19-C3;A9-B19-C4; A9-B19-C5; A9-B19-C6; A9-B19-C7; A9-B19-C8; A9-B19-C9;A9-B19-C10; A9-B19-C11; A9-B19-C12; A9-B19-C13; A9-B19-C14; A9-B19-C15;A9-B19-C16; A9-B19-C17; A9-B19-C18; A9-B19-C19; A9-B19-C20; A9-B19-C21;A9-B19-C22; A9-B19-C23; A9-B19-C24; A9-B19-C25; A9-B19-C26; A9-B19-C27;A9-B19-C28; A9-B19-C29; A9-B19-C30; A9-B19-C31; A9-B19-C32; A9-B19-C33;A9-B19-C34; A9-B19-C35; A9-B19-C36; A9-B19-C37; A9-B19-C38; A9-B19-C39;A9-B19-C40; A9-B19-C41; A9-B19-C42; A9-B19-C43; A9-B19-C44; A9-B19-C45;A9-B19-C46; A10-B19-C1; A10-B19-C2; A10-B19-C3; A10-B19-C4; A10-B19-C5;A10-B19-C6; A10-B19-C7; A10-B19-C8; A10-B19-C9; A10-B19-C10;A10-B19-C11; A10-B19-C12; A10-B19-C13; A10-B19-C14; A10-B19-C15;A10-B19-C16; A10-B19-C17; A10-B19-C18; A10-B19-C19; A10-B19-C20;A10-B19-C21; A10-B19-C22; A10-B19-C23; A10-B19-C24; A10-B19-C25;A10-B19-C26; A10-B19-C27; A10-B19-C28; A10-B19-C29; A10-B19-C30;A10-B19-C31; A10-B19-C32; A10-B19-C33; A10-B19-C34; A10-B19-C35;A10-B19-C36; A10-B19-C37; A10-B19-C38; A10-B19-C39; A10-B19-C40;A10-B19-C41; A10-B19-C42; A10-B19-C43; A10-B19-C44; A10-B19-C45;A10-B19-C46; A11-B19-C1; A11-B19-C2; A11-B19-C3; A11-B19-C4; A11-B19-C5;A11-B19-C6; A11-B19-C7; A11-B19-C8; A11-B19-C9; A11-B19-C10;A11-B19-C11; A11-B19-C12; A11-B19-C13; A11-B19-C14; A11-B19-C15;A11-B19-C16; A11-B19-C17; A11-B19-C18; A11-B19-C19; A11-B19-C20;A11-B19-C21; A11-B19-C22; A11-B19-C23; A11-B19-C24; A11-B19-C25;A11-B19-C26; A11-B19-C27; A11-B19-C28; A11-B19-C29; A11-B19-C30;A11-B19-C31; A11-B19-C32; A11-B19-C33; A11-B19-C34; A11-B19-C35;A11-B19-C36; A11-B19-C37; A11-B19-C38; A11-B19-C39; A11-B19-C40;A11-B19-C41; A11-B19-C42; A11-B19-C43; A11-B19-C44; A11-B19-C45;A11-B19-C46; A12-B19-C1; A12-B19-C2; A12-B19-C3; A12-B19-C4; A12-B19-C5;A12-B19-C6; A12-B19-C7; A12-B19-C8; A12-B19-C9; A12-B19-C10;A12-B19-C11; A12-B19-C12; A12-B19-C13; A12-B19-C14; A12-B19-C15;A12-B19-C16; A12-B19-C17; A12-B19-C18; A12-B19-C19; A12-B19-C20;A12-B19-C21; A12-B19-C22; A12-B19-C23; A12-B19-C24; A12-B19-C25;A12-B19-C26; A12-B19-C27; A12-B19-C28; A12-B19-C29; A12-B19-C30;A12-B19-C31; A12-B19-C32; A12-B19-C33; A12-B19-C34; A12-B19-C35;A12-B19-C36; A12-B19-C37; A12-B19-C38; A12-B19-C39; A12-B19-C40;A12-B19-C41; A12-B19-C42; A12-B19-C43; A12-B19-C44; A12-B19-C45;A12-B19-C46; A13-B19-C1; A13-B19-C2; A13-B19-C3; A13-B19-C4; A13-B19-C5;A13-B19-C6; A13-B19-C7; A13-B19-C8; A13-B19-C9; A13-B19-C10;A13-B19-C11; A13-B19-C12; A13-B19-C13; A13-B19-C14; A13-B19-C15;A13-B19-C16; A13-B19-C17; A13-B19-C18; A13-B19-C19; A13-B19-C20;A13-B19-C21; A13-B19-C22; A13-B19-C23; A13-B19-C24; A13-B19-C25;A13-B19-C26; A13-B19-C27; A13-B19-C28; A13-B19-C29; A13-B19-C30;A13-B19-C31; A13-B19-C32; A13-B19-C33; A13-B19-C34; A13-B19-C35;A13-B19-C36; A13-B19-C37; A13-B19-C38; A13-B19-C39; A13-B19-C40;A13-B19-C41; A13-B19-C42; A13-B19-C43; A13-B19-C44; A13-B19-C45;A13-B19-C46; A14-B19-C1; A14-B19-C2; A14-B19-C3; A14-B19-C4; A14-B19-C5;A14-B19-C6; A14-B19-C7; A14-B19-C8; A14-B19-C9; A14-B19-C10;A14-B19-C11; A14-B19-C12; A14-B19-C13; A14-B19-C14; A14-B19-C15;A14-B19-C16; A14-B19-C17; A14-B19-C18; A14-B19-C19; A14-B19-C20;A14-B19-C21; A14-B19-C22; A14-B19-C23; A14-B19-C24; A14-B19-C25;A14-B19-C26; A14-B19-C27; A14-B19-C28; A14-B19-C29; A14-B19-C30;A14-B19-C31; A14-B19-C32; A14-B19-C33; A14-B19-C34; A14-B19-C35;A14-B19-C36; A14-B19-C37; A14-B19-C38; A14-B19-C39; A14-B19-C40;A14-B19-C41; A14-B19-C42; A14-B19-C43; A14-B19-C44; A14-B19-C45;A14-B19-C46; A15-B19-C1; A15-B19-C2; A15-B19-C3; A15-B19-C4; A15-B19-C5;A15-B19-C6; A15-B19-C7; A15-B19-C8; A15-B19-C9; A15-B19-C10;A15-B19-C11; A15-B19-C12; A15-B19-C13; A15-B19-C14; A15-B19-C15;A15-B19-C16; A15-B19-C17; A15-B19-C18; A15-B19-C19; A15-B19-C20;A15-B19-C21; A15-B19-C22; A15-B19-C23; A15-B19-C24; A15-B19-C25;A15-B19-C26; A15-B19-C27; A15-B19-C28; A15-B19-C29; A15-B19-C30;A15-B19-C31; A15-B19-C32; A15-B19-C33; A15-B19-C34; A15-B19-C35;A15-B19-C36; A15-B19-C37; A15-B19-C38; A15-B19-C39; A15-B19-C40;A15-B19-C41; A15-B19-C42; A15-B19-C43; A15-B19-C44; A15-B19-C45;A15-B19-C46; A16-B19-C1; A16-B19-C2; A16-B19-C3; A16-B19-C4; A16-B19-C5;A16-B19-C6; A16-B19-C7; A16-B19-C8; A16-B19-C9; A16-B19-C10;A16-B19-C11; A16-B19-C12; A16-B19-C13; A16-B19-C14; A16-B19-C15;A16-B19-C16; A16-B19-C17; A16-B19-C18; A16-B19-C19; A16-B19-C20;A16-B19-C21; A16-B19-C22; A16-B19-C23; A16-B19-C24; A16-B19-C25;A16-B19-C26; A16-B19-C27; A16-B19-C28; A16-B19-C29; A16-B19-C30;A16-B19-C31; A16-B19-C32; A16-B19-C33; A16-B19-C34; A16-B19-C35;A16-B19-C36; A16-B19-C37; A16-B19-C38; A16-B19-C39; A16-B19-C40;A16-B19-C41; A16-B19-C42; A16-B19-C43; A16-B19-C44; A16-B19-C45;A16-B19-C46; A17-B19-C1; A17-B19-C2; A17-B19-C3; A17-B19-C4; A17-B19-C5;A17-B19-C6; A17-B19-C7; A17-B19-C8; A17-B19-C9; A17-B19-C10;A17-B19-C11; A17-B19-C12; A17-B19-C13; A17-B19-C14; A17-B19-C15;A17-B19-C16; A17-B19-C17; A17-B19-C18; A17-B19-C19; A17-B19-C20;A17-B19-C21; A17-B19-C22; A17-B19-C23; A17-B19-C24; A17-B19-C25;A17-B19-C26; A17-B19-C27; A17-B19-C28; A17-B19-C29; A17-B19-C30;A17-B19-C31; A17-B19-C32; A17-B19-C33; A17-B19-C34; A17-B19-C35;A17-B19-C36; A17-B19-C37; A17-B19-C38; A17-B19-C39; A17-B19-C40;A17-B19-C41; A17-B19-C42; A17-B19-C43; A17-B19-C44; A17-B19-C45;A17-B19-C46; A18-B19-C1; A18-B19-C2; A18-B19-C3; A18-B19-C4; A18-B19-C5;A18-B19-C6; A18-B19-C7; A18-B19-C8; A18-B19-C9; A18-B19-C10;A18-B19-C11; A18-B19-C12; A18-B19-C13; A18-B19-C14; A18-B19-C15;A18-B19-C16; A18-B19-C17; A18-B19-C18; A18-B19-C19; A18-B19-C20;A18-B19-C21; A18-B19-C22; A18-B19-C23; A18-B19-C24; A18-B19-C25;A18-B19-C26; A18-B19-C27; A18-B19-C28; A18-B19-C29; A18-B19-C30;A18-B19-C31; A18-B19-C32; A18-B19-C33; A18-B19-C34; A18-B19-C35;A18-B19-C36; A18-B19-C37; A18-B19-C38; A18-B19-C39; A18-B19-C40;A18-B19-C41; A18-B19-C42; A18-B19-C43; A18-B19-C44; A18-B19-C45;A18-B19-C46; A19-B19-C1; A19-B19-C2; A19-B19-C3; A19-B19-C4; A19-B19-C5;A19-B19-C6; A19-B19-C7; A19-B19-C8; A19-B19-C9; 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A26-B19-C8; A26-B19-C9; A26-B19-C10;A26-B19-C11; A26-B19-C12; A26-B19-C13; A26-B19-C14; A26-B19-C15;A26-B19-C16; A26-B19-C17; A26-B19-C18; A26-B19-C19; A26-B19-C20;A26-B19-C21; A26-B19-C22; A26-B19-C23; A26-B19-C24; A26-B19-C25;A26-B19-C26; A26-B19-C27; A26-B19-C28; A26-B19-C29; A26-B19-C30;A26-B19-C31; A26-B19-C32; A26-B19-C33; A26-B19-C34; A26-B19-C35;A26-B19-C36; A26-B19-C37; A26-B19-C38; A26-B19-C39; A26-B19-C40;A26-B19-C41; A26-B19-C42; A26-B19-C43; A26-B19-C44; A26-B19-C45;A26-B19-C46; A27-B19-C1; A27-B19-C2; A27-B19-C3; A27-B19-C4; A27-B19-C5;A27-B19-C6; A27-B19-C7; A27-B19-C8; A27-B19-C9; A27-B19-C10;A27-B19-C11; A27-B19-C12; A27-B19-C13; A27-B19-C14; A27-B19-C15;A27-B19-C16; A27-B19-C17; A27-B19-C18; A27-B19-C19; A27-B19-C20;A27-B19-C21; A27-B19-C22; A27-B19-C23; A27-B19-C24; A27-B19-C25;A27-B19-C26; A27-B19-C27; A27-B19-C28; A27-B19-C29; A27-B19-C30;A27-B19-C31; A27-B19-C32; A27-B19-C33; A27-B19-C34; A27-B19-C35;A27-B19-C36; A27-B19-C37; A27-B19-C38; A27-B19-C39; A27-B19-C40;A27-B19-C41; 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A19-B20-C32; A19-B20-C33; A19-B20-C34; A19-B20-C35;A19-B20-C36; A19-B20-C37; A19-B20-C38; A19-B20-C39; A19-B20-C40;A19-B20-C41; A19-B20-C42; A19-B20-C43; A19-B20-C44; A19-B20-C45;A19-B20-C46; A20-B20-C1; A20-B20-C2; A20-B20-C3; A20-B20-C4; A20-B20-C5;A20-B20-C6; A20-B20-C7; A20-B20-C8; A20-B20-C9; A20-B20-C10;A20-B20-C11; A20-B20-C12; A20-B20-C13; A20-B20-C14; A20-B20-C15;A20-B20-C16; A20-B20-C17; A20-B20-C18; A20-B20-C19; A20-B20-C20;A20-B20-C21; A20-B20-C22; A20-B20-C23; A20-B20-C24; A20-B20-C25;A20-B20-C26; A20-B20-C27; A20-B20-C28; A20-B20-C29; A20-B20-C30;A20-B20-C31; A20-B20-C32; A20-B20-C33; A20-B20-C34; A20-B20-C35;A20-B20-C36; A20-B20-C37; A20-B20-C38; A20-B20-C39; A20-B20-C40;A20-B20-C41; A20-B20-C42; A20-B20-C43; A20-B20-C44; A20-B20-C45;A20-B20-C46; A21-B20-C1; A21-B20-C2; A21-B20-C3; A21-B20-C4; A21-B20-C5;A21-B20-C6; A21-B20-C7; A21-B20-C8; A21-B20-C9; A21-B20-C10;A21-B20-C11; A21-B20-C12; A21-B20-C13; A21-B20-C14; A21-B20-C15;A21-B20-C16; A21-B20-C17; A21-B20-C18; A21-B20-C19; A21-B20-C20;A21-B20-C21; A21-B20-C22; A21-B20-C23; A21-B20-C24; A21-B20-C25;A21-B20-C26; A21-B20-C27; A21-B20-C28; A21-B20-C29; A21-B20-C30;A21-B20-C31; A21-B20-C32; A21-B20-C33; A21-B20-C34; A21-B20-C35;A21-B20-C36; A21-B20-C37; A21-B20-C38; A21-B20-C39; A21-B20-C40;A21-B20-C41; A21-B20-C42; A21-B20-C43; A21-B20-C44; A21-B20-C45;A21-B20-C46; A22-B20-C1; A22-B20-C2; A22-B20-C3; A22-B20-C4; A22-B20-C5;A22-B20-C6; A22-B20-C7; A22-B20-C8; A22-B20-C9; A22-B20-C10;A22-B20-C11; A22-B20-C12; A22-B20-C13; A22-B20-C14; A22-B20-C15;A22-B20-C16; A22-B20-C17; A22-B20-C18; A22-B20-C19; A22-B20-C20;A22-B20-C21; A22-B20-C22; A22-B20-C23; A22-B20-C24; A22-B20-C25;A22-B20-C26; A22-B20-C27; A22-B20-C28; A22-B20-C29; A22-B20-C30;A22-B20-C31; A22-B20-C32; A22-B20-C33; A22-B20-C34; A22-B20-C35;A22-B20-C36; A22-B20-C37; A22-B20-C38; A22-B20-C39; A22-B20-C40;A22-B20-C41; A22-B20-C42; A22-B20-C43; A22-B20-C44; A22-B20-C45;A22-B20-C46; A23-B20-C1; A23-B20-C2; A23-B20-C3; A23-B20-C4; A23-B20-C5;A23-B20-C6; A23-B20-C7; A23-B20-C8; A23-B20-C9; A23-B20-C10;A23-B20-C11; A23-B20-C12; A23-B20-C13; A23-B20-C14; A23-B20-C15;A23-B20-C16; A23-B20-C17; A23-B20-C18; A23-B20-C19; A23-B20-C20;A23-B20-C21; A23-B20-C22; A23-B20-C23; A23-B20-C24; A23-B20-C25;A23-B20-C26; A23-B20-C27; A23-B20-C28; A23-B20-C29; A23-B20-C30;A23-B20-C31; A23-B20-C32; A23-B20-C33; A23-B20-C34; A23-B20-C35;A23-B20-C36; A23-B20-C37; A23-B20-C38; A23-B20-C39; A23-B20-C40;A23-B20-C41; A23-B20-C42; A23-B20-C43; A23-B20-C44; A23-B20-C45;A23-B20-C46; A24-B20-C1; A24-B20-C2; A24-B20-C3; A24-B20-C4; A24-B20-C5;A24-B20-C6; A24-B20-C7; A24-B20-C8; A24-B20-C9; A24-B20-C10;A24-B20-C11; A24-B20-C12; A24-B20-C13; A24-B20-C14; A24-B20-C15;A24-B20-C16; A24-B20-C17; A24-B20-C18; A24-B20-C19; A24-B20-C20;A24-B20-C21; A24-B20-C22; A24-B20-C23; A24-B20-C24; A24-B20-C25;A24-B20-C26; A24-B20-C27; A24-B20-C28; A24-B20-C29; A24-B20-C30;A24-B20-C31; A24-B20-C32; A24-B20-C33; A24-B20-C34; A24-B20-C35;A24-B20-C36; A24-B20-C37; A24-B20-C38; A24-B20-C39; A24-B20-C40;A24-B20-C41; A24-B20-C42; A24-B20-C43; A24-B20-C44; A24-B20-C45;A24-B20-C46; A25-B20-C1; A25-B20-C2; A25-B20-C3; A25-B20-C4; A25-B20-C5;A25-B20-C6; A25-B20-C7; A25-B20-C8; A25-B20-C9; A25-B20-C10;A25-B20-C11; A25-B20-C12; A25-B20-C13; A25-B20-C14; A25-B20-C15;A25-B20-C16; A25-B20-C17; A25-B20-C18; A25-B20-C19; A25-B20-C20;A25-B20-C21; A25-B20-C22; A25-B20-C23; A25-B20-C24; A25-B20-C25;A25-B20-C26; A25-B20-C27; A25-B20-C28; A25-B20-C29; A25-B20-C30;A25-B20-C31; A25-B20-C32; A25-B20-C33; A25-B20-C34; A25-B20-C35;A25-B20-C36; A25-B20-C37; A25-B20-C38; A25-B20-C39; A25-B20-C40;A25-B20-C41; A25-B20-C42; A25-B20-C43; A25-B20-C44; A25-B20-C45;A25-B20-C46; A26-B20-C1; A26-B20-C2; A26-B20-C3; A26-B20-C4; A26-B20-C5;A26-B20-C6; A26-B20-C7; A26-B20-C8; A26-B20-C9; A26-B20-C10;A26-B20-C11; A26-B20-C12; A26-B20-C13; A26-B20-C14; A26-B20-C15;A26-B20-C16; A26-B20-C17; A26-B20-C18; A26-B20-C19; A26-B20-C20;A26-B20-C21; A26-B20-C22; A26-B20-C23; A26-B20-C24; A26-B20-C25;A26-B20-C26; A26-B20-C27; A26-B20-C28; A26-B20-C29; A26-B20-C30;A26-B20-C31; A26-B20-C32; A26-B20-C33; A26-B20-C34; A26-B20-C35;A26-B20-C36; A26-B20-C37; A26-B20-C38; A26-B20-C39; A26-B20-C40;A26-B20-C41; A26-B20-C42; A26-B20-C43; A26-B20-C44; A26-B20-C45;A26-B20-C46; A27-B20-C1; A27-B20-C2; A27-B20-C3; A27-B20-C4; A27-B20-C5;A27-B20-C6; A27-B20-C7; A27-B20-C8; A27-B20-C9; A27-B20-C10;A27-B20-C11; A27-B20-C12; A27-B20-C13; A27-B20-C14; A27-B20-C15;A27-B20-C16; A27-B20-C17; A27-B20-C18; A27-B20-C19; A27-B20-C20;A27-B20-C21; A27-B20-C22; A27-B20-C23; A27-B20-C24; A27-B20-C25;A27-B20-C26; A27-B20-C27; A27-B20-C28; A27-B20-C29; A27-B20-C30;A27-B20-C31; A27-B20-C32; A27-B20-C33; A27-B20-C34; A27-B20-C35;A27-B20-C36; A27-B20-C37; A27-B20-C38; A27-B20-C39; A27-B20-C40;A27-B20-C41; A27-B20-C42; A27-B20-C43; A27-B20-C44; A27-B20-C45;A27-B20-C46; A28-B20-C1; A28-B20-C2; A28-B20-C3; A28-B20-C4; A28-B20-C5;A28-B20-C6; A28-B20-C7; A28-B20-C8; A28-B20-C9; A28-B20-C10;A28-B20-C11; A28-B20-C12; A28-B20-C13; A28-B20-C14; A28-B20-C15;A28-B20-C16; A28-B20-C17; A28-B20-C18; A28-B20-C19; A28-B20-C20;A28-B20-C21; A28-B20-C22; A28-B20-C23; A28-B20-C24; A28-B20-C25;A28-B20-C26; A28-B20-C27; A28-B20-C28; A28-B20-C29; A28-B20-C30;A28-B20-C31; A28-B20-C32; A28-B20-C33; A28-B20-C34; A28-B20-C35;A28-B20-C36; A28-B20-C37; A28-B20-C38; A28-B20-C39; A28-B20-C40;A28-B20-C41; A28-B20-C42; A28-B20-C43; A28-B20-C44; A28-B20-C45;A28-B20-C46; A1-B21-C1; A1-B21-C2; A1-B21-C3; A1-B21-C4; A1-B21-C5;A1-B21-C6; A1-B21-C7; A1-B21-C8; A1-B21-C9; A1-B21-C10; A1-B21-C11;A1-B21-C12; A1-B21-C13; A1-B21-C14; A1-B21-C15; A1-B21-C16; A1-B21-C17;A1-B21-C18; A1-B21-C19; A1-B21-C20; A1-B21-C21; A1-B21-C22; A1-B21-C23;A1-B21-C24; A1-B21-C25; A1-B21-C26; A1-B21-C27; A1-B21-C28; A1-B21-C29;A1-B21-C30; A1-B21-C31; A1-B21-C32; A1-B21-C33; A1-B21-C34; A1-B21-C35;A1-B21-C36; A1-B21-C37; A1-B21-C38; A1-B21-C39; A1-B21-C40; A1-B21-C41;A1-B21-C42; A1-B21-C43; A1-B21-C44; A1-B21-C45; A1-B21-C46; A2-B21-C1;A2-B21-C2; A2-B21-C3; A2-B21-C4; A2-B21-C5; A2-B21-C6; A2-B21-C7;A2-B21-C8; A2-B21-C9; A2-B21-C10; A2-B21-C11; A2-B21-C12; A2-B21-C13;A2-B21-C14; A2-B21-C15; A2-B21-C16; A2-B21-C17; A2-B21-C18; A2-B21-C19;A2-B21-C20; A2-B21-C21; A2-B21-C22; A2-B21-C23; A2-B21-C24; A2-B21-C25;A2-B21-C26; A2-B21-C27; A2-B21-C28; A2-B21-C29; A2-B21-C30; A2-B21-C31;A2-B21-C32; A2-B21-C33; A2-B21-C34; A2-B21-C35; A2-B21-C36; A2-B21-C37;A2-B21-C38; A2-B21-C39; A2-B21-C40; A2-B21-C41; A2-B21-C42; A2-B21-C43;A2-B21-C44; A2-B21-C45; A2-B21-C46; A3-B21-C1; A3-B21-C2; A3-B21-C3;A3-B21-C4; A3-B21-C5; A3-B21-C6; A3-B21-C7; A3-B21-C8; A3-B21-C9;A3-B21-C10; A3-B21-C11; A3-B21-C12; A3-B21-C13; A3-B21-C14; A3-B21-C15;A3-B21-C16; A3-B21-C17; A3-B21-C18; A3-B21-C19; A3-B21-C20; A3-B21-C21;A3-B21-C22; A3-B21-C23; A3-B21-C24; A3-B21-C25; A3-B21-C26; A3-B21-C27;A3-B21-C28; A3-B21-C29; A3-B21-C30; A3-B21-C31; A3-B21-C32; A3-B21-C33;A3-B21-C34; A3-B21-C35; A3-B21-C36; A3-B21-C37; A3-B21-C38; A3-B21-C39;A3-B21-C40; A3-B21-C41; A3-B21-C42; A3-B21-C43; A3-B21-C44; A3-B21-C45;A3-B21-C46; A4-B21-C1; A4-B21-C2; A4-B21-C3; A4-B21-C4; A4-B21-C5;A4-B21-C6; A4-B21-C7; A4-B21-C8; A4-B21-C9; A4-B21-C10; A4-B21-C11;A4-B21-C12; A4-B21-C13; A4-B21-C14; A4-B21-C15; A4-B21-C16; A4-B21-C17;A4-B21-C18; A4-B21-C19; A4-B21-C20; A4-B21-C21; A4-B21-C22; A4-B21-C23;A4-B21-C24; A4-B21-C25; A4-B21-C26; A4-B21-C27; A4-B21-C28; A4-B21-C29;A4-B21-C30; A4-B21-C31; A4-B21-C32; A4-B21-C33; A4-B21-C34; A4-B21-C35;A4-B21-C36; A4-B21-C37; A4-B21-C38; A4-B21-C39; A4-B21-C40; A4-B21-C41;A4-B21-C42; A4-B21-C43; A4-B21-C44; A4-B21-C45; A4-B21-C46; A5-B21-C1;A5-B21-C2; A5-B21-C3; A5-B21-C4; A5-B21-C5; A5-B21-C6; A5-B21-C7;A5-B21-C8; A5-B21-C9; A5-B21-C10; A5-B21-C11; A5-B21-C12; A5-B21-C13;A5-B21-C14; A5-B21-C15; A5-B21-C16; A5-B21-C17; A5-B21-C18; A5-B21-C19;A5-B21-C20; A5-B21-C21; A5-B21-C22; A5-B21-C23; A5-B21-C24; A5-B21-C25;A5-B21-C26; A5-B21-C27; A5-B21-C28; A5-B21-C29; A5-B21-C30; A5-B21-C31;A5-B21-C32; A5-B21-C33; A5-B21-C34; A5-B21-C35; A5-B21-C36; A5-B21-C37;A5-B21-C38; A5-B21-C39; A5-B21-C40; A5-B21-C41; A5-B21-C42; A5-B21-C43;A5-B21-C44; A5-B21-C45; A5-B21-C46; A6-B21-C1; A6-B21-C2; A6-B21-C3;A6-B21-C4; A6-B21-C5; A6-B21-C6; A6-B21-C7; A6-B21-C8; A6-B21-C9;A6-B21-C10; A6-B21-C11; A6-B21-C12; A6-B21-C13; A6-B21-C14; A6-B21-C15;A6-B21-C16; A6-B21-C17; A6-B21-C18; A6-B21-C19; A6-B21-C20; A6-B21-C21;A6-B21-C22; A6-B21-C23; A6-B21-C24; A6-B21-C25; A6-B21-C26; A6-B21-C27;A6-B21-C28; A6-B21-C29; A6-B21-C30; A6-B21-C31; A6-B21-C32; A6-B21-C33;A6-B21-C34; A6-B21-C35; A6-B21-C36; A6-B21-C37; A6-B21-C38; A6-B21-C39;A6-B21-C40; A6-B21-C41; A6-B21-C42; A6-B21-C43; A6-B21-C44; A6-B21-C45;A6-B21-C46; A7-B21-C1; A7-B21-C2; A7-B21-C3; A7-B21-C4; A7-B21-C5;A7-B21-C6; A7-B21-C7; A7-B21-C8; A7-B21-C9; A7-B21-C10; A7-B21-C11;A7-B21-C12; A7-B21-C13; A7-B21-C14; A7-B21-C15; A7-B21-C16; A7-B21-C17;A7-B21-C18; A7-B21-C19; A7-B21-C20; A7-B21-C21; A7-B21-C22; A7-B21-C23;A7-B21-C24; A7-B21-C25; A7-B21-C26; A7-B21-C27; A7-B21-C28; A7-B21-C29;A7-B21-C30; A7-B21-C31; A7-B21-C32; A7-B21-C33; A7-B21-C34; A7-B21-C35;A7-B21-C36; A7-B21-C37; A7-B21-C38; A7-B21-C39; A7-B21-C40; A7-B21-C41;A7-B21-C42; A7-B21-C43; A7-B21-C44; A7-B21-C45; A7-B21-C46; A8-B21-C1;A8-B21-C2; A8-B21-C3; A8-B21-C4; A8-B21-C5; A8-B21-C6; A8-B21-C7;A8-B21-C8; A8-B21-C9; A8-B21-C10; A8-B21-C11; A8-B21-C12; A8-B21-C13;A8-B21-C14; A8-B21-C15; A8-B21-C16; A8-B21-C17; A8-B21-C18; A8-B21-C19;A8-B21-C20; A8-B21-C21; A8-B21-C22; A8-B21-C23; A8-B21-C24; A8-B21-C25;A8-B21-C26; A8-B21-C27; A8-B21-C28; A8-B21-C29; A8-B21-C30; A8-B21-C31;A8-B21-C32; A8-B21-C33; A8-B21-C34; A8-B21-C35; A8-B21-C36; A8-B21-C37;A8-B21-C38; A8-B21-C39; A8-B21-C40; A8-B21-C41; A8-B21-C42; A8-B21-C43;A8-B21-C44; A8-B21-C45; A8-B21-C46; A9-B21-C1; A9-B21-C2; A9-B21-C3;A9-B21-C4; A9-B21-C5; A9-B21-C6; A9-B21-C7; A9-B21-C8; A9-B21-C9;A9-B21-C10; A9-B21-C11; A9-B21-C12; A9-B21-C13; A9-B21-C14; A9-B21-C15;A9-B21-C16; A9-B21-C17; A9-B21-C18; A9-B21-C19; A9-B21-C20; A9-B21-C21;A9-B21-C22; A9-B21-C23; A9-B21-C24; A9-B21-C25; A9-B21-C26; A9-B21-C27;A9-B21-C28; A9-B21-C29; A9-B21-C30; A9-B21-C31; A9-B21-C32; A9-B21-C33;A9-B21-C34; A9-B21-C35; A9-B21-C36; A9-B21-C37; A9-B21-C38; A9-B21-C39;A9-B21-C40; A9-B21-C41; A9-B21-C42; A9-B21-C43; A9-B21-C44; A9-B21-C45;A9-B21-C46; A10-B21-C1; A10-B21-C2; A10-B21-C3; A10-B21-C4; A10-B21-C5;A10-B21-C6; A10-B21-C7; A10-B21-C8; A10-B21-C9; A10-B21-C10;A10-B21-C11; A10-B21-C12; A10-B21-C13; A10-B21-C14; A10-B21-C15;A10-B21-C16; A10-B21-C17; A10-B21-C18; A10-B21-C19; A10-B21-C20;A10-B21-C21; A10-B21-C22; A10-B21-C23; A10-B21-C24; A10-B21-C25;A10-B21-C26; A10-B21-C27; A10-B21-C28; A10-B21-C29; A10-B21-C30;A10-B21-C31; A10-B21-C32; A10-B21-C33; A10-B21-C34; A10-B21-C35;A10-B21-C36; A10-B21-C37; A10-B21-C38; A10-B21-C39; A10-B21-C40;A10-B21-C41; A10-B21-C42; A10-B21-C43; A10-B21-C44; A10-B21-C45;A10-B21-C46; A11-B21-C1; A11-B21-C2; A11-B21-C3; A11-B21-C4; A11-B21-C5;A11-B21-C6; A11-B21-C7; A11-B21-C8; A11-B21-C9; A11-B21-C10;A11-B21-C11; A11-B21-C12; A11-B21-C13; A11-B21-C14; A11-B21-C15;A11-B21-C16; A11-B21-C17; A11-B21-C18; A11-B21-C19; A11-B21-C20;A11-B21-C21; A11-B21-C22; A11-B21-C23; A11-B21-C24; A11-B21-C25;A11-B21-C26; A11-B21-C27; A11-B21-C28; A11-B21-C29; A11-B21-C30;A11-B21-C31; A11-B21-C32; A11-B21-C33; A11-B21-C34; A11-B21-C35;A11-B21-C36; A11-B21-C37; A11-B21-C38; A11-B21-C39; A11-B21-C40;A11-B21-C41; A11-B21-C42; A11-B21-C43; A11-B21-C44; A11-B21-C45;A11-B21-C46; A12-B21-C1; A12-B21-C2; A12-B21-C3; A12-B21-C4; A12-B21-C5;A12-B21-C6; A12-B21-C7; A12-B21-C8; A12-B21-C9; A12-B21-C10;A12-B21-C11; A12-B21-C12; A12-B21-C13; A12-B21-C14; A12-B21-C15;A12-B21-C16; A12-B21-C17; A12-B21-C18; A12-B21-C19; A12-B21-C20;A12-B21-C21; A12-B21-C22; A12-B21-C23; A12-B21-C24; A12-B21-C25;A12-B21-C26; A12-B21-C27; A12-B21-C28; A12-B21-C29; A12-B21-C30;A12-B21-C31; A12-B21-C32; A12-B21-C33; A12-B21-C34; A12-B21-C35;A12-B21-C36; A12-B21-C37; A12-B21-C38; A12-B21-C39; A12-B21-C40;A12-B21-C41; A12-B21-C42; A12-B21-C43; A12-B21-C44; A12-B21-C45;A12-B21-C46; A13-B21-C1; A13-B21-C2; A13-B21-C3; A13-B21-C4; A13-B21-C5;A13-B21-C6; A13-B21-C7; A13-B21-C8; A13-B21-C9; A13-B21-C10;A13-B21-C11; A13-B21-C12; A13-B21-C13; A13-B21-C14; A13-B21-C15;A13-B21-C16; A13-B21-C17; A13-B21-C18; A13-B21-C19; A13-B21-C20;A13-B21-C21; A13-B21-C22; A13-B21-C23; A13-B21-C24; A13-B21-C25;A13-B21-C26; A13-B21-C27; A13-B21-C28; A13-B21-C29; A13-B21-C30;A13-B21-C31; A13-B21-C32; A13-B21-C33; A13-B21-C34; A13-B21-C35;A13-B21-C36; A13-B21-C37; A13-B21-C38; A13-B21-C39; A13-B21-C40;A13-B21-C41; A13-B21-C42; A13-B21-C43; A13-B21-C44; A13-B21-C45;A13-B21-C46; A14-B21-C1; A14-B21-C2; A14-B21-C3; A14-B21-C4; A14-B21-C5;A14-B21-C6; A14-B21-C7; A14-B21-C8; A14-B21-C9; A14-B21-C10;A14-B21-C11; A14-B21-C12; A14-B21-C13; A14-B21-C14; A14-B21-C15;A14-B21-C16; A14-B21-C17; A14-B21-C18; A14-B21-C19; A14-B21-C20;A14-B21-C21; A14-B21-C22; A14-B21-C23; A14-B21-C24; A14-B21-C25;A14-B21-C26; A14-B21-C27; A14-B21-C28; A14-B21-C29; A14-B21-C30;A14-B21-C31; A14-B21-C32; A14-B21-C33; A14-B21-C34; A14-B21-C35;A14-B21-C36; A14-B21-C37; A14-B21-C38; A14-B21-C39; A14-B21-C40;A14-B21-C41; A14-B21-C42; A14-B21-C43; A14-B21-C44; A14-B21-C45;A14-B21-C46; A15-B21-C1; A15-B21-C2; A15-B21-C3; A15-B21-C4; A15-B21-C5;A15-B21-C6; A15-B21-C7; A15-B21-C8; A15-B21-C9; A15-B21-C10;A15-B21-C11; A15-B21-C12; A15-B21-C13; A15-B21-C14; A15-B21-C15;A15-B21-C16; A15-B21-C17; A15-B21-C18; A15-B21-C19; A15-B21-C20;A15-B21-C21; A15-B21-C22; A15-B21-C23; A15-B21-C24; A15-B21-C25;A15-B21-C26; A15-B21-C27; A15-B21-C28; A15-B21-C29; A15-B21-C30;A15-B21-C31; A15-B21-C32; A15-B21-C33; A15-B21-C34; A15-B21-C35;A15-B21-C36; A15-B21-C37; A15-B21-C38; A15-B21-C39; A15-B21-C40;A15-B21-C41; A15-B21-C42; A15-B21-C43; A15-B21-C44; A15-B21-C45;A15-B21-C46; A16-B21-C1; A16-B21-C2; A16-B21-C3; A16-B21-C4; A16-B21-C5;A16-B21-C6; A16-B21-C7; A16-B21-C8; A16-B21-C9; A16-B21-C10;A16-B21-C11; A16-B21-C12; A16-B21-C13; A16-B21-C14; A16-B21-C15;A16-B21-C16; A16-B21-C17; A16-B21-C18; A16-B21-C19; A16-B21-C20;A16-B21-C21; A16-B21-C22; A16-B21-C23; A16-B21-C24; A16-B21-C25;A16-B21-C26; A16-B21-C27; A16-B21-C28; A16-B21-C29; A16-B21-C30;A16-B21-C31; A16-B21-C32; A16-B21-C33; A16-B21-C34; A16-B21-C35;A16-B21-C36; A16-B21-C37; A16-B21-C38; A16-B21-C39; A16-B21-C40;A16-B21-C41; A16-B21-C42; A16-B21-C43; A16-B21-C44; A16-B21-C45;A16-B21-C46; A17-B21-C1; A17-B21-C2; A17-B21-C3; A17-B21-C4; A17-B21-C5;A17-B21-C6; A17-B21-C7; A17-B21-C8; A17-B21-C9; A17-B21-C10;A17-B21-C11; A17-B21-C12; A17-B21-C13; A17-B21-C14; A17-B21-C15;A17-B21-C16; A17-B21-C17; A17-B21-C18; A17-B21-C19; A17-B21-C20;A17-B21-C21; A17-B21-C22; A17-B21-C23; A17-B21-C24; A17-B21-C25;A17-B21-C26; A17-B21-C27; A17-B21-C28; A17-B21-C29; A17-B21-C30;A17-B21-C31; A17-B21-C32; A17-B21-C33; A17-B21-C34; A17-B21-C35;A17-B21-C36; A17-B21-C37; A17-B21-C38; A17-B21-C39; A17-B21-C40;A17-B21-C41; A17-B21-C42; A17-B21-C43; A17-B21-C44; A17-B21-C45;A17-B21-C46; A18-B21-C1; A18-B21-C2; A18-B21-C3; A18-B21-C4; A18-B21-C5;A18-B21-C6; A18-B21-C7; A18-B21-C8; A18-B21-C9; A18-B21-C10;A18-B21-C11; A18-B21-C12; A18-B21-C13; A18-B21-C14; A18-B21-C15;A18-B21-C16; A18-B21-C17; A18-B21-C18; A18-B21-C19; 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A20-B21-C8; A20-B21-C9; A20-B21-C10;A20-B21-C11; A20-B21-C12; A20-B21-C13; A20-B21-C14; A20-B21-C15;A20-B21-C16; A20-B21-C17; A20-B21-C18; A20-B21-C19; A20-B21-C20;A20-B21-C21; A20-B21-C22; A20-B21-C23; A20-B21-C24; A20-B21-C25;A20-B21-C26; A20-B21-C27; A20-B21-C28; A20-B21-C29; A20-B21-C30;A20-B21-C31; A20-B21-C32; A20-B21-C33; A20-B21-C34; A20-B21-C35;A20-B21-C36; A20-B21-C37; A20-B21-C38; A20-B21-C39; A20-B21-C40;A20-B21-C41; A20-B21-C42; A20-B21-C43; A20-B21-C44; A20-B21-C45;A20-B21-C46; A21-B21-C1; A21-B21-C2; A21-B21-C3; A21-B21-C4; A21-B21-C5;A21-B21-C6; A21-B21-C7; A21-B21-C8; A21-B21-C9; A21-B21-C10;A21-B21-C11; A21-B21-C12; A21-B21-C13; A21-B21-C14; A21-B21-C15;A21-B21-C16; A21-B21-C17; A21-B21-C18; A21-B21-C19; A21-B21-C20;A21-B21-C21; A21-B21-C22; A21-B21-C23; A21-B21-C24; A21-B21-C25;A21-B21-C26; A21-B21-C27; A21-B21-C28; A21-B21-C29; A21-B21-C30;A21-B21-C31; A21-B21-C32; A21-B21-C33; A21-B21-C34; A21-B21-C35;A21-B21-C36; A21-B21-C37; A21-B21-C38; A21-B21-C39; A21-B21-C40;A21-B21-C41; A21-B21-C42; A21-B21-C43; A21-B21-C44; A21-B21-C45;A21-B21-C46; A22-B21-C1; A22-B21-C2; A22-B21-C3; A22-B21-C4; A22-B21-C5;A22-B21-C6; A22-B21-C7; A22-B21-C8; A22-B21-C9; A22-B21-C10;A22-B21-C11; A22-B21-C12; A22-B21-C13; A22-B21-C14; A22-B21-C15;A22-B21-C16; A22-B21-C17; A22-B21-C18; A22-B21-C19; A22-B21-C20;A22-B21-C21; A22-B21-C22; A22-B21-C23; A22-B21-C24; A22-B21-C25;A22-B21-C26; A22-B21-C27; A22-B21-C28; A22-B21-C29; A22-B21-C30;A22-B21-C31; A22-B21-C32; A22-B21-C33; A22-B21-C34; A22-B21-C35;A22-B21-C36; A22-B21-C37; A22-B21-C38; A22-B21-C39; A22-B21-C40;A22-B21-C41; A22-B21-C42; A22-B21-C43; A22-B21-C44; A22-B21-C45;A22-B21-C46; A23-B21-C1; A23-B21-C2; A23-B21-C3; A23-B21-C4; A23-B21-C5;A23-B21-C6; A23-B21-C7; A23-B21-C8; A23-B21-C9; A23-B21-C10;A23-B21-C11; A23-B21-C12; A23-B21-C13; A23-B21-C14; A23-B21-C15;A23-B21-C16; A23-B21-C17; A23-B21-C18; A23-B21-C19; A23-B21-C20;A23-B21-C21; A23-B21-C22; A23-B21-C23; A23-B21-C24; A23-B21-C25;A23-B21-C26; A23-B21-C27; A23-B21-C28; A23-B21-C29; A23-B21-C30;A23-B21-C31; A23-B21-C32; A23-B21-C33; A23-B21-C34; A23-B21-C35;A23-B21-C36; A23-B21-C37; A23-B21-C38; A23-B21-C39; A23-B21-C40;A23-B21-C41; A23-B21-C42; A23-B21-C43; A23-B21-C44; A23-B21-C45;A23-B21-C46; A24-B21-C1; A24-B21-C2; A24-B21-C3; A24-B21-C4; A24-B21-C5;A24-B21-C6; A24-B21-C7; A24-B21-C8; A24-B21-C9; A24-B21-C10;A24-B21-C11; A24-B21-C12; A24-B21-C13; A24-B21-C14; A24-B21-C15;A24-B21-C16; A24-B21-C17; A24-B21-C18; A24-B21-C19; A24-B21-C20;A24-B21-C21; A24-B21-C22; A24-B21-C23; A24-B21-C24; A24-B21-C25;A24-B21-C26; A24-B21-C27; A24-B21-C28; A24-B21-C29; A24-B21-C30;A24-B21-C31; A24-B21-C32; A24-B21-C33; A24-B21-C34; A24-B21-C35;A24-B21-C36; A24-B21-C37; A24-B21-C38; A24-B21-C39; A24-B21-C40;A24-B21-C41; A24-B21-C42; A24-B21-C43; A24-B21-C44; A24-B21-C45;A24-B21-C46; A25-B21-C1; A25-B21-C2; A25-B21-C3; A25-B21-C4; A25-B21-C5;A25-B21-C6; A25-B21-C7; A25-B21-C8; A25-B21-C9; A25-B21-C10;A25-B21-C11; A25-B21-C12; A25-B21-C13; A25-B21-C14; A25-B21-C15;A25-B21-C16; A25-B21-C17; A25-B21-C18; A25-B21-C19; A25-B21-C20;A25-B21-C21; A25-B21-C22; A25-B21-C23; A25-B21-C24; A25-B21-C25;A25-B21-C26; A25-B21-C27; A25-B21-C28; A25-B21-C29; A25-B21-C30;A25-B21-C31; A25-B21-C32; A25-B21-C33; A25-B21-C34; A25-B21-C35;A25-B21-C36; A25-B21-C37; A25-B21-C38; A25-B21-C39; A25-B21-C40;A25-B21-C41; A25-B21-C42; A25-B21-C43; A25-B21-C44; A25-B21-C45;A25-B21-C46; A26-B21-C1; A26-B21-C2; A26-B21-C3; A26-B21-C4; A26-B21-C5;A26-B21-C6; A26-B21-C7; A26-B21-C8; A26-B21-C9; A26-B21-C10;A26-B21-C11; A26-B21-C12; A26-B21-C13; A26-B21-C14; A26-B21-C15;A26-B21-C16; A26-B21-C17; A26-B21-C18; A26-B21-C19; A26-B21-C20;A26-B21-C21; A26-B21-C22; A26-B21-C23; A26-B21-C24; A26-B21-C25;A26-B21-C26; A26-B21-C27; A26-B21-C28; A26-B21-C29; A26-B21-C30;A26-B21-C31; A26-B21-C32; A26-B21-C33; A26-B21-C34; A26-B21-C35;A26-B21-C36; A26-B21-C37; A26-B21-C38; A26-B21-C39; A26-B21-C40;A26-B21-C41; A26-B21-C42; A26-B21-C43; A26-B21-C44; A26-B21-C45;A26-B21-C46; A27-B21-C1; A27-B21-C2; A27-B21-C3; A27-B21-C4; A27-B21-C5;A27-B21-C6; A27-B21-C7; A27-B21-C8; A27-B21-C9; A27-B21-C10;A27-B21-C11; A27-B21-C12; A27-B21-C13; A27-B21-C14; A27-B21-C15;A27-B21-C16; A27-B21-C17; A27-B21-C18; A27-B21-C19; A27-B21-C20;A27-B21-C21; A27-B21-C22; A27-B21-C23; A27-B21-C24; A27-B21-C25;A27-B21-C26; A27-B21-C27; A27-B21-C28; A27-B21-C29; A27-B21-C30;A27-B21-C31; A27-B21-C32; A27-B21-C33; A27-B21-C34; A27-B21-C35;A27-B21-C36; A27-B21-C37; A27-B21-C38; A27-B21-C39; A27-B21-C40;A27-B21-C41; A27-B21-C42; A27-B21-C43; A27-B21-C44; A27-B21-C45;A27-B21-C46; A28-B21-C1; A28-B21-C2; A28-B21-C3; A28-B21-C4; A28-B21-C5;A28-B21-C6; A28-B21-C7; A28-B21-C8; A28-B21-C9; A28-B21-C10;A28-B21-C11; A28-B21-C12; A28-B21-C13; A28-B21-C14; A28-B21-C15;A28-B21-C16; A28-B21-C17; A28-B21-C18; A28-B21-C19; A28-B21-C20;A28-B21-C21; A28-B21-C22; A28-B21-C23; A28-B21-C24; A28-B21-C25;A28-B21-C26; A28-B21-C27; A28-B21-C28; A28-B21-C29; A28-B21-C30;A28-B21-C31; A28-B21-C32; A28-B21-C33; A28-B21-C34; A28-B21-C35;A28-B21-C36; A28-B21-C37; A28-B21-C38; A28-B21-C39; A28-B21-C40;A28-B21-C41; A28-B21-C42; A28-B21-C43; A28-B21-C44; A28-B21-C45;A28-B21-C46; A1-B22; A2-B22; A3-B22; A4-B22; A5-B22; A6-B22; A7-B22;A8-B22; A9-B22; A10-B22; A11-B22; A12-B22; A13-B22; A14-B22; A15-B22;A16-B22; A17-B22; A18-B22; A19-B22; A20-B22; A21-B22; A22-B22; A23-B22;A24-B22; A25-B22; A26-B22; A27-B22; A28-B22; A1-B23; A2-B23; A3-B23;A4-B23; A5-B23; A6-B23; A7-B23; A8-B23; A9-B23; A10-B23; A11-B23;A12-B23; A13-B23; A14-B23; A15-B23; A16-B23; A17-B23; A18-B23; A19-B23;A20-B23; A21-B23; A22-B23; A23-B23; A24-B23; A25-B23; A26-B23; A27-B23;A28-B23; A1-B24; A2-B24; A3-B24; A4-B24; A5-B24; A6-B24; A7-B24; A8-B24;A9-B24; A10-B24; A11-B24; A12-B24; A13-B24; A14-B24; A15-B24; A16-B24;A17-B24; A18-B24; A19-B24; A20-B24; A21-B24; A22-B24; A23-B24; A24-B24;A25-B24; A26-B24; A27-B24; A28-B24; A1-B25; A2-B25; A3-B25; A4-B25;A5-B25; A6-B25; A7-B25; A8-B25; A9-B25; A10-B25; A11-B25; A12-B25;A13-B25; A14-B25; A15-B25; A16-B25; A17-B25; A18-B25; A19-B25; A20-B25;A21-B25; A22-B25; A23-B25; A24-B25; A25-B25; A26-B25; A27-B25; A28-B25;A1-B26; A2-B26; A3-B26; A4-B26; A5-B26; A6-B26; A7-B26; A8-B26; A9-B26;A10-B26; A11-B26; A12-B26; A13-B26; A14-B26; A15-B26; A16-B26; A17-B26;A18-B26; A19-B26; A20-B26; A21-B26; A22-B26; A23-B26; A24-B26; A25-B26;A26-B26; A27-B26; A28-B26; A1-B27; A2-B27; A3-B27; A4-B27; A5-B27;A6-B27; A7-B27; A8-B27; A9-B27; A10-B27; A11-B27; A12-B27; A13-B27;A14-B27; A15-B27; A16-B27; A17-B27; A18-B27; A19-B27; A20-B27; A21-B27;A22-B27; A23-B27; A24-B27; A25-B27; A26-B27; A27-B27; A28-B27; A1-B28;A2-B28; A3-B28; A4-B28; A5-B28; A6-B28; A7-B28; A8-B28; A9-B28; A10-B28;A11-B28; A12-B28; A13-B28; A14-B28; A15-B28; A16-B28; A17-B28; A18-B28;A19-B28; A20-B28; A21-B28; A22-B28; A23-B28; A24-B28; A25-B28; A26-B28;A27-B28; A28-B28; A1-B29; A2-B29; A3-B29; A4-B29; A5-B29; A6-B29;A7-B29; A8-B29; A9-B29; A10-B29; A11-B29; A12-B29; A13-B29; A14-B29;A15-B29; A16-B29; A17-B29; A18-B29; A19-B29; A20-B29; A21-B29; A22-B29;A23-B29; A24-B29; A25-B29; A26-B29; A27-B29; A28-B29; A1-B30; A2-B30;A3-B30; A4-B30; A5-B30; A6-B30; A7-B30; A8-B30; A9-B30; A10-B30;A11-B30; A12-B30; A13-B30; A14-B30; A15-B30; A16-B30; A17-B30; A18-B30;A19-B30; A20-B30; A21-B30; A22-B30; A23-B30; A24-B30; A25-B30; A26-B30;A27-B30; A28-B30; A1-B31; A2-B31; A3-B31; A4-B31; A5-B31; A6-B31;A7-B31; A8-B31; A9-B31; A10-B31; A11-B31; A12-B31; A13-B31; A14-B31;A15-B31; A16-B31; A17-B31; A18-B31; A19-B31; A20-B31; A21-B31; A22-B31;A23-B31; A24-B31; A25-B31; A26-B31; A27-B31; A28-B31; A1-B32; A2-B32;A3-B32; A4-B32; A5-B32; A6-B32; A7-B32; A8-B32; A9-B32; A10-B32;A11-B32; A12-B32; A13-B32; A14-B32; A15-B32; A16-B32; A17-B32; A18-B32;A19-B32; A20-B32; A21-B32; A22-B32; A23-B32; A24-B32; A25-B32; A26-B32;A27-B32; A28-B32; A29-B33; A30-B33; A31-B33; A32-B33; A33-B33; A34-B33;A35-B33; A36-B33; A37-B33; A38-B33; A39-B33; A40-B33; A41-B33; A29-B34;A30-B34; A31-B34; A32-B34; A33-B34; A34-B34; A35-B34; A36-B34; A37-B34;A38-B34; A39-B34; A40-B34; A41-B34; A29-B35; A30-B35; A31-B35; A32-B35;A33-B35; A34-B35; A35-B35; A36-B35; A37-B35; A38-B35; A39-B35; A40-B35;A41-B35; A29-B36; A30-B36; A31-B36; A32-B36; A33-B36; A34-B36; A35-B36;A36-B36; A37-B36; A38-B36; A39-B36; A40-B36; A41-B36; A29-B37; A30-B37;A31-B37; A32-B37; A33-B37; A34-B37; A35-B37; A36-B37; A37-B37; A38-B37;A39-B37; A40-B37; A41-B37; A29-B38; A30-B38; A31-B38; A32-B38; A33-B38;A34-B38; A35-B38; A36-B38; A37-B38; A38-B38; A39-B38; A40-B38; A41-B38;A29-B39; A30-B39; A31-B39; A32-B39; A33-B39; A34-B39; A35-B39; A36-B39;A37-B39; A38-B39; A39-B39; A40-B39; A41-B39; A29-B40; A30-B40; A31-B40;A32-B40; A33-B40; A34-B40; A35-B40; A36-B40; A37-B40; A38-B40; A39-B40;A40-B40; A41-B40; A29-B41; A30-B41; A31-B41; A32-B41; A33-B41; A34-B41;A35-B41; A36-B41; A37-B41; A38-B41; A39-B41; A40-B41; A41-B41; A29-B42;A30-B42; A31-B42; A32-B42; A33-B42; A34-B42; A35-B42; A36-B42; A37-B42;A38-B42; A39-B42; A40-B42; A41-B42; A29-B43; A30-B43; A31-B43; A32-B43;A33-B43; A34-B43; A35-B43; A36-B43; A37-B43; A38-B43; A39-B43; A40-B43;A41-B43; A29-B44; A30-B44; A31-B44; A32-B44; A33-B44; A34-B44; A35-B44;A36-B44; A37-B44; A38-B44; A39-B44; A40-B44; A41-B44.

[0192] Thus, for example, in the above list the compound denoted asA1-B1-C1 is the product of the combination of group A1 in Table 1 and B1in Table 2 and C1 in Table 3, namely

[0193] Example 1(a) hereinafter described.

[0194] Particular compounds of the invention are:

[0195] 6-(5-methoxy-1-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine;

[0196] 6-(1-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine;

[0197] 6-(3-bromophenyl)-5H-pyrrolo[2,3-b]pyrazine;

[0198] 7-iso-propyl-6-phenyl-5H-pyrrolo[2,3-b]pyrazine;

[0199] 2-(4-bromophenyl)-1H-pyrrolo[2,3-b]pyrazine;

[0200] 6-(4-[1,3]dioxan-2-yl-phenyl)-5H-pyrrolo[2,3-b]pyrazine;

[0201] 6-(3-[1,3]dioxan-2-yl-phenyl)-5H-pyrrolo[2,3-b]pyrazine;

[0202] 2-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-quinoline;

[0203] 3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-isoquinoline;

[0204] 6-[1-methyl-1H-indol-5-yl]-5H-pyrrolo[2,3-b]pyrazine;

[0205]6-(5-methoxy-1-methyl-1H-indol-3-yl)-2-methyl-5H-pyrrolo[2,3-b]pyrazine;

[0206] 3-methyl-6-(1-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine;

[0207] 6-(1-benzyl-5-methoxy-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine;

[0208] 6-(1-methyl-1H-pyrrol-3-yl)-5H-pyrrolo[2,3-b]pyrazine;

[0209] 6-(1-methyl-1H-pyrrol-2-yl)-5H-pyrrolo[2,3-b]pyrazine;

[0210] 6-indolizin-1-yl-5H-pyrrolo[2,3-b]pyrazine;

[0211] 6-(3-methyl-indolizin-1-yl)-5H-pyrrolo[2,3-b]pyrazine;

[0212] 6-(3-methyl-5-phenyl-1H-pyrrol-3-yl)-5H-pyrrolo[2,3-b]pyrazine;

[0213] 6-(5,6,7,8-tetrahydro-indolizin-1yl)-5H-pyrrolo[2,3-b]pyrazine;

[0214] 6-furan-3-yl-5H-pyrrolo[2,3-b]pyrazine;

[0215] dimethyl-[4-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-phenyl]-amine;

[0216]6-(5-methoxy-1-methyl-1H-indol-3-yl)-7-methyl-5H-pyrrolo[2,3-b]pyrazine;

[0217] 6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazine;

[0218] 6-(4-tert-butylphenyl)-7-methyl-5H-pyrrolo[2,3-b]pyrazine;

[0219] 6-(3,4-dimethoxyphenyl)-5H-pyrrolo[2,3-b]pyrazine;

[0220] 6-(4-aminophenyl)-7-methyl-5H-pyrrolo[2,3-b]pyrazine;

[0221] 6-[4-(1-methyl)ethoxyphenyl]-5H-pyrrolo[2,3-b]pyrazine;

[0222]6-(1H-1-methyl-2-(methylthio)imidazol-5-yl)-5H-pyrrolo[2,3-b]pyrazine;

[0223] 6-(1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine;

[0224] 6-(4-fluorophenyl)-5H-pyrrolo[2,3-b]pyrazine;

[0225] 6-(4-methoxyphenyl)-5H-pyrrolo[2,3-b]pyrazine;

[0226]7-(prop-2-enyl)-6-[4-(tert-butyl)phenyl]-5H-pyrrolo[2,3-b]pyrazine;

[0227] 6-(4-methylthiophenyl)-5H-pyrrolo[2,3-b]pyrazine;

[0228] 6-(3-methoxylphenyl)-5H-pyrrolo[2,3-b]pyrazine;

[0229] 6-(1-methyl-1H-pyrazol-4-yl)-5H-pyrrolo[2,3-b]pyrazine;

[0230] 6-(1-methyl-5-phenyl-1H-pyrazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine;

[0231] 6-(pyridin-2-yl)-5H-pyrrolo[2,3-b]pyrazine;

[0232] 6-(pyridin-4-yl)-5H-pyrrolo[2,3-b]pyrazine;

[0233] 3-[3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-indol-1-yl]-propan-1-ol;

[0234]3-[5-methoxy-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-indol-1-yl]-propan-1-ol;

[0235] 2-[3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-indol-1-yl]-ethanol;

[0236]2-[5-methoxy-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-indol-1-yl]-ethanol;

[0237] 3-[3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-indol-1-yl]-propylamine;

[0238]3-[5-methoxy-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-indol-1-yl]-propylamine;

[0239]N-{3-[3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-indol-1-yl]-propyl}-acetamide;

[0240]6-[1-(3-morpholin-4-yl-propyl)-1H-indol-3-yl]-5H-pyrrolo[2,3-b]pyrazine;

[0241]6-[1-(3-piperidin-1-yl-propyl)-1H-indol-3-yl]-5H-pyrrolo[2,3-b]pyrazine;

[0242]6-{1-[3-(pyridin-3-yloxy)-propyl]-1H-indol-3-yl}-5H-pyrrolo[2,3-b]pyrazine;

[0243] 1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indol-5-ol;

[0244]6-(2-chloro-5-methoxy-1-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine;

[0245] 3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-benzaldehyde;

[0246] 4-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-benzaldehyde;

[0247] [3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-phenyl]-methanol;

[0248] [4-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-phenyl]-methanol;

[0249] 6-(5-methoxy-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine;

[0250]2-[5-methoxy-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-indol-1-yl]-1-morpholin-4-yl-ethanone;

[0251] [5-methoxy-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-indol-1-yl]-aceticacid;

[0252]4-methoxy-2-(5-methoxy-3-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridine;

[0253] 4-methoxy-2-(5-methoxy-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridine;

[0254] 4-chloro-2-(4-tertiary-butylphenyll)-1H-pyrrolo[2,3-b]pyridine;

[0255]5-phenyl-2-(5-methoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridine;

[0256]2-[5-methoxy-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-indol-1-yl]-1-morpholin-4-yl-ethanone;

[0257]1-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yloxy]-cyclobutanecarboxylicacid amide;

[0258]1-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yloxy]-cyclobutanecarboxylicacid methylamide;

[0259] 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylicacid methylamide;

[0260] 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylicacid (2-hydroxy-ethyl)-amide;

[0261] 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylicacid (2-morpholin-4-yl-ethyl)-amide;

[0262] 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylicacid (2-carbamoyl-ethyl)-amide;

[0263] 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylicacid bis-(2-hydroxy-ethyl)-amide;

[0264] 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylicacid amide;

[0265] 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylicacid (2-hydroxy-1,1-bis-hydroxymethyl-ethyl)-amide;

[0266] 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylicacid (2-hydroxy-1-hydroxymethyl-1-methyl-ethyl)-amide;

[0267] 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylicacid (2,3-dihydroxy-propyl)-amide;

[0268] 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylicacid (2-hydroxy-1,1-dimethylethyl)-amide;

[0269] 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yI)-1H-indole-5-carboxylicacid (2-hydroxy-1-hydroxymethyl-ethyl)-amide;

[0270] 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-6-carboxylicacid (2-carbamoyl-ethyl)-amide;

[0271] 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-6-carboxylicacid (2-hydroxy-ethyl)-amide;

[0272] 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-6-carboxylicacid (1H-[1,2,4]triazol-3-yl)-amide;

[0273] 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-6-carboxylicacid (2-hydroxy-1-hydroxymethyl-ethyl)-amide;

[0274] 1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylicacid (2-hydroxy-1,1-dimethyl-ethyl)-amide;

[0275]3-[6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-N-methylpropionamide;

[0276]3-[6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-N,N-dimethylpropionamide;

[0277] 1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylicacid 2-methoxyethylamide;

[0278] 1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylicacid 2-thien-2-ylethylamide;

[0279] 1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylicacid 2-fluoroethylamide;

[0280] 1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylicacid 2-carboethoxyethylamide;

[0281] 1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylicacid (hydroxymethyl)-carbomethoxy-methylamide;

[0282] 1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylicacid 2-hydroxyethylamide;

[0283] 1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylicacid methylamide;

[0284] 1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylicacid dimethylamide;

[0285][1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indol-5-yl]morpholin-4-ylketone;

[0286]4-hydroxy-[1-[1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indol-5-yl]carbonylpiperidine

[0287]3-[1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indol-5-yl]carbonylaminopropionicacid methylamide;

[0288] 1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylicacid 3-hydroxypropylamide;

[0289]3-{6-[4-(1-methyl)ethoxyphenyl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}propionicacid methylamide;

[0290] 3-[6-(4-methoxyphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propionicacid methylamide;

[0291]3-{6-[4-(1-methyl)ethoxyphenyl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}propionamide;

[0292]3-{6-(4-hydroxyphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl}propionamide;

[0293] 3-[6-(4-fluorophenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propionicacid methylamide;

[0294][1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yloxy]-aceticacid;

[0295]2-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yloxy]-propionicacid;

[0296]1-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yloxy]-cyclobutanecarboxylicacid;

[0297] 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylicacid;

[0298] 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-ol;

[0299] 1-{1-(cyclobutanecarboxylicacid)-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-cyclobutanecarboxylicacid;

[0300] 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-6-carboxylicacid;

[0301]3-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yl]-propionicacid;

[0302] 1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylicacid;

[0303] [2-methoxy-5-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-phenoxy]acetic acid;

[0304]3-[2-dimethylamino-5-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-phenyl]propionicacid;

[0305]2-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yloxy]-ethanol;

[0306]2-[-methyl-3-(1H-pyrrolo[2,3-b]pyrdin-2-yl)-1H-indol-5-yloxyl-propan-1-ol;

[0307]{1-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yloxy]-cyclobutyl}-methanol;

[0308] 2-(6-phenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl)-ethanol;

[0309]3-[1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indol-5-yl]carbonylaminopropionicacid;

[0310] 2-[2-methoxy-5-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-phenoxy]-ethanol;

[0311]3-[2-dimethylamino-5-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-phenyl]-propan-1-ol;

[0312]3-{6-[4-(1-methyl)ethoxyphenyl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}propanol;

[0313] 2-(5-methoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridine;

[0314]3-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yloxy]-propane-1,2-diol;

[0315]3-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yloxy]-propan-1-ol;

[0316]3-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yloxy]-propan-2-ol;

[0317]2-[1-methyl-5-(2H-tetrazol-5-yl)-1H-indol-3-yl]-1H-pyrrolo[2,3-b]pyridine;

[0318]2-[1-methyl-5-(2-methyl-2H-tetrazol-5-yl)-1H-indol-3-yl]-1H-pyrrolo[2,3-b]pyridine;

[0319]2-[1-methyl-5-(1-methyl-1H-tetrazol-5-yl)-1H-indol-3-yl]-1H-pyrrolo[2,3-b]pyridine;

[0320]1-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yl]-ethanone;

[0321]2-(5,6-dimethoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridine;

[0322]2-[5-(2-methoxy-1-methyl-ethoxy)-1-methyl-1H-indol-3-yl]-1H-pyrrolo[2,3-b]pyridine;

[0323]2-[1-methyl-5-(5-methyl-[1,2,4]oxadiazol-3-yl)-1H-indol-3-yl]-1H-pyrrolo[2,3-b]pyridine;

[0324]3-[6-methoxy-1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yloxy]-propane-1,2-diol;

[0325]6-methoxy-1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-ol;

[0326]2-(5-methoxy-1-methyl-1H-indol-3-yl)-4-phenyl-1H-pyrrolo[2,3-b]pyridine;

[0327]2-[5-(pyridin-4-yl)-1-methyl-1H-indol-3-yl]-1H-pyrrolo[2,3-b]pyridine;

[0328]2-(5-methoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile;

[0329]4-chloro-2-(5-methoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridine;

[0330] 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-ylamine;

[0331]N-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yl]-methanesulfonamide;

[0332]N-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yl]-acetamide;

[0333]{1-[5-(1-hydroxymethyl-cyclobutoxy)-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-indol-1-yl]-cyclobutyl}-methanol;

[0334]{1-[1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indol-5-yloxy]-cyclobutyl}-methanol;

[0335]2-[6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]ethyl-2H-tetrazole;

[0336]3-[6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2H-propionitrile;

[0337]3-[6-(4-tert-butylphenyl-5-pyrrolo[2,3-b]pyrazin-7-yl]-propionamide;

[0338]3-[6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propionic acid;

[0339]3-{6-[4-(1-methyl)ethoxyphenyl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}propionicacid;

[0340] 3-[6-(4-fluorophenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propionicacid;

[0341] 3-[6-(4-methoxyphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propionicacid;

[0342]3-[6-(4-tert-butyl-phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propan-1-ol;

[0343] [2-methoxy-5-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-phenoxy]acetic acidethyl ester;

[0344] 2-methoxy-5-(5H-pyrrolo[2,3-b]pyrazin-6-yl)phenol;

[0345]3-fluoro-2-(5-methoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridine;

[0346] 3-{6-(4-hydroxyphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl}propionicacid;

[0347] ethyl3-{6-(4-hydroxyphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl}propionate;

[0348]2-(5-methoxy-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile;

[0349] 6-(4-methylsulfinylphenyl)-5H-pyrrolo[2,3-b]pyrazine;

[0350] 6-(4-methylsulfonylphenyl)-5H-pyrrolo[2,3-b]pyrazine;

[0351]3-(6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)propylamine;

[0352]N-{3-(6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)propyl}acetamide;

[0353]N-{3-(6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)propyl}cyclopropylcarboxylicacid amide;

[0354]N-{3-(6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)propyl}butyramide;

[0355]N-{3-(6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)propyl}methoxyacetamide;

[0356]N-{3-(6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)propyl}thien-2ylcarboxylicacid amide;

[0357]N-{3-(6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)propyl}-N′-propylurea;

[0358]N-{3-(6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)propyl}-N′-carboethoxymethylurea;

[0359]N-{3-(6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)propyl}-N′,N′-diethylurea;

[0360]N-{3-(6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)propyl}methanesulfonamide;

[0361]N-{3-(6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)propyl}thien-2-ylsulfonamide

[0362]N-{3-(6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)propyl}dimethylisoxazol-4-ylsulfonamide;

[0363]N-{3-(6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)propyl}1-methylimidazol-4-ylsulfonamide;

[0364] and the corresponding N-oxides, and their prodrugs; andpharmaceutically acceptable salts and solvates (e.g. hydrates) of suchcompounds and their N-oxides and prodrugs.

[0365] Preferred compounds of the invention are:

[0366] 6-(5-methoxy-1-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine(compound denoted as A1-B1-C1);

[0367]1-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yloxy]-cyclobutanecarboxylicacid amide(compound denoted as A2-B1-C31);

[0368]2-(5-methoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile(compounddenoted as A3-B1-C28);

[0369]{1-[1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indol-5-yloxy]-cyclobutyl}-methanol(compounddenoted as A1-B1-C28);

[0370] and the corresponding N-oxides, and their prodrugs; andpharmaceutically acceptable salts and solvates (e.g. hydrates) of suchcompounds and their N-oxides and prodrugs.

[0371] The compounds of the invention exhibit useful pharmacologicalactivity and accordingly are incorporated into pharmaceuticalcompositions and used in the treatment of patients suffering fromcertain medical disorders. The present invention thus provides,according to a further aspect, compounds of the invention andcompositions containing compounds of the invention for use in therapy.

[0372] Compounds within the scope of the present invention block kinasecatalytic activity according to tests described in the literature anddescribed in vitro procedures hereinafter, and which tests results arebelieved to correlate to pharmacological activity in humans and othermammals. Thus, in a further embodiment, the present invention providescompounds of the invention and compositions containing compounds of theinvention for use in the treatment of a patient suffering from, orsubject to, conditions which can be ameliorated by the administration ofprotein kinase inhibitors (e.g. Syk, FAK, KDR or Aurora2). For example,compounds of the present invention are useful in the treatment ofinflammatory diseases, for example asthma: inflammatory dermatoses (e.g.psoriasis, dematitis herpetiformis, eczema, necrotizing and cutaneousvasculitis, bullous disease); allergic rhinitis and allergicconjunctivitis; joint inflammation, including arthritis, rheumatoidarthritis and other arthritic conditions such as rheumatoid spondylitis,gouty arthritis, traumatic arthritis, rubella arthritis, psoriaticarthritis and osteoarthritis. The compounds are also useful in thetreatment of Chronic Obstructive Pulmonary Disease (COPD), acutesynovitis, autoimmune diabetes, autoimmune encephalomyelitis, collitis,atherosclerosis, peripheral vascular disease, cardiovascular disease,multiple sclerosis, restenosis, myocarditis, B cell lymphomas, systemiclupus erythematosus, graft v host disease and other transplantassociated rejection events, cancers and tumours (such as colorectal,prostate, breast, thyroid, colon and lung cancers) and inflammatorybowel disease. Additionally, the compounds are useful as tumoranti-angiogenic agents.

[0373] A special embodiment of the therapeutic methods of the presentinvention is the treating of asthma.

[0374] Another special embodiment of the therapeutic methods of thepresent invention is the treating of psoriasis

[0375] Another special embodiment of the therapeutic methods of thepresent invention is the treating of joint inflammation.

[0376] Another special embodiment of the therapeutic methods of thepresent invention is the treating of inflammatory bowel disease.

[0377] A special embodiment of the therapeutic methods of the presentinvention is the treating of cancers and tumours.

[0378] According to a further feature of the invention there is provideda method for the treatment of a human or animal patient suffering from,or subject to, conditions which can be ameliorated by the administrationof a protein kinase inhibitor (e.g. Syk, FAK, KDR or Aurora2) forexample conditions as hereinbefore described, which comprises theadministration to the patient of an effective amount of compound of theinvention or a composition containing a compound of the invention.“Effective amount” is meant to describe an amount of compound of thepresent invention effective in inhibiting the catalytic activity aprotein kinase, such as Syk, FAK, KDR or Aurora2, and thus producing thedesired therapeutic effect.

[0379] References herein to treatment should be understood to includeprophylactic therapy as well as treatment of established conditions.

[0380] The present invention also includes within its scopepharmaceutical compositions comprising at least one of the compounds ofthe invention in association with a pharmaceutically acceptable carrieror excipient.

[0381] Compounds of the invention may be administered by any suitablemeans. In practice compounds of the present invention may generally beadministered parenterally, topically, rectally, orally or by inhalation,especially by the oral route.

[0382] Compositions according to the invention may be prepared accordingto the customary methods, using one or more pharmaceutically acceptableadjuvants or excipients. The adjuvants comprise, inter alia, diluents,sterile aqueous media and the various non-toxic organic solvents. Thecompositions may be presented in the form of tablets, pills, granules,powders, aqueous solutions or suspensions, injectable solutions, elixirsor syrups, and can contain one or more agents chosen from the groupcomprising sweeteners, flavourings, colourings, or stabilisers in orderto obtain pharmaceutically acceptable preparations. The choice ofvehicle and the content of active substance in the vehicle are generallydetermined in accordance with the solubility and chemical properties ofthe active compound, the particular mode of administration and theprovisions to be observed in pharmaceutical practice. For example,excipients such as lactose, sodium citrate, calcium carbonate, dicalciumphosphate and disintegrating agents such as starch, alginic acids andcertain complex silicates combined with lubricants such as magnesiumstearate, sodium lauryl sulfate and talc may be used for preparingtablets. To prepare a capsule, it is advantageous to use lactose andhigh molecular weight polyethylene glycols. When aqueous suspensions areused they can contain emulsifying agents or agents which facilitatesuspension. Diluents such as sucrose, ethanol, polyethylene glycol,propylene glycol, glycerol and chloroform or mixtures thereof may alsobe used.

[0383] For parenteral administration, emulsions, suspensions orsolutions of the products according to the invention in vegetable oil,for example sesame oil, groundnut oil or olive oil, or aqueous-organicsolutions such as water and propylene glycol, injectable organic esterssuch as ethyl oleate, as well as sterile aqueous solutions of thepharmaceutically acceptable salts, are used. The solutions of the saltsof the products according to the invention are especially useful foradministration by intramuscular or subcutaneous injection. The aqueoussolutions, also comprising solutions of the salts in pure distilledwater, may be used for intravenous administration with the proviso thattheir pH is suitably adjusted, that they are judiciously buffered andrendered isotonic with a sufficient quantity of glucose or sodiumchloride and that they are sterilised by heating, irradiation ormicrofiltration.

[0384] For topical administration, gels (water or alcohol based), creamsor ointments containing compounds of the invention may be used.Compounds of the invention may also be incorporated in a gel or matrixbase for application in a patch, which would allow a controlled releaseof compound through the transdermal barrier.

[0385] For administration by inhalation compounds of the invention maybe dissolved or suspended in a suitable carrier for use in a nebuliseror a suspension or solution aerosol, or may be absorbed or adsorbed ontoa suitable solid carrier for use in a dry powder inhaler.

[0386] Solid compositions for rectal administration includesuppositories formulated in accordance with known methods and containingat least one compound of the invention.

[0387] The percentage of active ingredient in the compositions of theinvention may be varied, it being necessary that it should constitute aproportion such that a suitable dosage shall be obtained. Obviously,several unit dosage forms may be administered at about the same time.The dose employed will be determined by the physician, and depends uponthe desired therapeutic effect, the route of administration and theduration of the treatment, and the condition of the patient. In theadult, the doses are generally from about 0.001 to about 50, preferablyabout 0.001 to about 5, mg/kg body weight per day by inhalation, fromabout 0.01 to about 100, preferably 0.1 to 70, more especially 0.5 to10, mg/kg body weight per day by oral administration, and from about0.001 to about 10, preferably 0.01 to 1, mg/kg body weight per day byintravenous administration. In each particular case, the doses will bedetermined in accordance with the factors distinctive to the subject tobe treated, such as age, weight, general state of health and othercharacteristics which can influence the efficacy of the medicinalproduct.

[0388] The compounds according to the invention may be administered asfrequently as necessary in order to obtain the desired therapeuticeffect. Some patients may respond rapidly to a higher or lower dose andmay find much weaker maintenance doses adequate. For other patients, itmay be necessary to have long-term treatments at the rate of 1 to 4doses per day, in accordance with the physiological requirements of eachparticular patient. Generally, the active product may be administeredorally 1 to 4 times per day. Of course, for some patients, it will benecessary to prescribe not more than one or two doses per day.

[0389] Compounds of the invention may be prepared by the application oradaptation of known methods, by which is meant methods used heretoforeor described in the literature, for example those described by R. C.Larock in Comprehensive Organic Transformations, VCH publishers, 1989.

[0390] In the reactions described hereinafter it may be necessary toprotect reactive functional groups, for example hydroxy, amino, imino,thio or carboxy groups, where these are desired in the final product, toavoid their unwanted participation in the reactions. Conventionalprotecting groups may be used in accordance with standard practice, forexamples see T. W. Greene and P. G. M. Wuts in “Protective Groups inOrganic Chemistry” John Wiley and Sons, 1991.

[0391] Compounds of formula (I) wherein R¹, R² and R³ are ashereinbefore defined, and X¹ is N or CH may be prepared by applicationor adaptation of the procedures described by Davis et al Tetrahedron,1992, 48, page 939-952, for example:

[0392] (i) reaction of compounds of formula (III):

[0393]  wherein R² and R³ are as hereinbefore defined and X¹ is N or CH,with a suitable base, such as lithium diisopropylamide (orbutyllithium), in an inert solvent, such as tetrahydrofuran, and at atemperature from about −26° C.;

[0394] (ii) treatment of the resulting anion with nitrites of formula(IV):

R¹—CN   (IV)

[0395]  wherein R¹ is as defined hereinbefore at a temperature at about−15° C. to about room temperature.

[0396] This procedure is particularly suitable for the preparation ofcompounds of formula (I) where R¹ is optionally substitutedN-methylindol-3-yl, R² and R³ are hydrogen and X¹ is N or CH.

[0397] Compounds of formula (I) wherein R¹, R², R³ and X¹ are ashereinbefore defined may also be prepared by application or adaptationof the procedure described by Chang and Bag, J.Org.Chem., 1995, 21,pages 7030-7032, for example reaction of compounds of formula (V):

[0398] wherein R¹, R², R³ and X¹ are as hereinbefore defined, and X² isa halogen, preferably iodine, atom or a triflate group, with a boronicacid of formula (VI):

R¹—B(OH)₂   (VI)

[0399] wherein R¹ is as defined hereinbefore. The coupling reaction mayconveniently be carried out for example in the presence of a complexmetal catalyst such as tetrakis(triphenylphosphine)palladium(0) andsodium bicarbonate, in aqueous dimethylformamide at a temperature up toreflux temperature.

[0400] Compounds of the invention may also be prepared byinterconversion of other compounds of the invention.

[0401] Thus, for example, compounds of formula (I) containing a carboxygroup may be prepared by hydrolysis of the corresponding esters. Thehydrolysis may conveniently be carried out by alkaline hydrolysis usinga base, such as an alkali metal hydroxide, e.g. lithium hydroxide, or analkali metal carbonate, e.g. potassium carbonate, in the presence of anaqueous/organic solvent mixture, using organic solvents such as dioxan,tetrahydrofuran or methanol, at a temperature from about ambient toabout reflux. The hydrolysis of the esters may also be carried out byacid hydrolysis using an inorganic acid, such as hydrochloric acid, inthe presence of an aqueous/inert organic solvent mixture, using organicsolvents such as dioxan or tetrahydrofuran, at a temperature from about50° C. to about 80° C.

[0402] As another example compounds of formula (I) containing a carboxygroup may be prepared by acid catalysed removal of the tert-butyl groupof the corresponding tert-butyl esters using standard reactionconditions, for example reaction with trifluoroacetic acid at atemperature at about room temperature.

[0403] As another example compounds of formula (I) containing a carboxygroup may be prepared by hydrogenation of the corresponding benzylesters. The reaction may be carried out in the presence of ammoniumformate and a suitable metal catalyst, e.g. palladium, supported on aninert carrier such as carbon, preferably in a solvent such as methanolor ethanol and at a temperature at about reflux temperature. Thereaction may alternatively be carried out in the presence of a suitablemetal catalyst, e.g. platinum or palladium optionally supported on aninert carrier such as carbon, preferably in a solvent such as methanolor ethanol.

[0404] As another example of the interconversion process, compounds offormula (I) containing a —C(═O)—NY¹Y² group may be prepared by couplingcompounds of formula (I) containing a carboxy group with an amine offormula HNY¹Y² to give an amide bond using standard peptide couplingprocedures, for example coupling in the presence ofO-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate and triethylamine (or diisopropylethylamine) intetrahydrofuran (or dimethylformamide) at room temperature. The couplingmay also be brought about by reaction of compounds of formula (I)containing a carboxy group withN-{(dimethylamino)(1H-1,2,3-triazaolo[4,5-b]pyridin-1-yl)methylene}-N-methylmethanaminiumhexafluorophosphate N-oxide in the presence of a suitable base, such asdiisopropylethylamine, in an inert solvent, such as dimethylformamide,and at a temperature at about room temperature, followed by reactionwith an amine of formula HNY¹Y² (ammonium chloride can be used for thepreparation of compounds of formula (I) containing a —C(═O)—NH₂ group).

[0405] As another example of the interconversion process, compounds offormula (I) containing a —CH₂OH group may be prepared by the reductionof corresponding compounds of formula (I) containing a —CHO or —CO₂R⁷(in which R⁷ is lower alkyl) group. For example, the reduction mayconveniently be carried out by means of reaction with lithium aluminiumhydride, in an inert solvent, such as tetrahydrofuran, and at atemperature from about room temperature to about reflux temperature.

[0406] As another example of the interconversion process, compounds offormula (I) in which R¹ is aryl or heteroaryl substituted by —CO₂Me maybe prepared by:

[0407] (i) treating compounds of formula (I) in which R¹ is aryl orheteroaryl substituted by hydroxy, withN-phenyltrifluoromethanesulfonimide in the presence of a suitable base,such as triethylamine, in an inert solvent, such as dichloromethane, andat a temperature at about −78° C.;

[0408] (ii) reaction of the resulting triflate with carbon monoxide inthe presence of a suitable catalyst (e.g. palladium acetate),1,3-bis(diphenylphosphino)propane, triethylamine and methanol, in aninert solvent, such as dimethylformamide at a pressure of about 1atmosphere, and at a temperature at about room temperature.

[0409] This procedure is particularly suitable for the preparation ofcompounds of formula (I) in which R¹ is5-carboxymethyl-N-methylindol-3-yl.

[0410] As another example of the interconversion process, compounds offormula (I) in which R¹ is aryl or heteroaryl substituted by —SO₂NY¹Y²may be prepared by:

[0411] (i) treating compounds of formula (I) in which R¹ is aryl orheteroaryl substituted by hydroxy, withN-phenyltrifluoromethanesulfonimide as described hereinabove;

[0412] (ii) treating the resulting triflate with tertiary-butylmercaptanin the presence of sodium tertiary-butoxide, palladium acetate, lithiumchloride and R(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl in aninert solvent, such as toluene, and at a temperature at about 110-120°C.;

[0413] (iii) reaction of the resulting compounds of formula (I) in whichR¹ is aryl or heteroaryl substituted by —S^(t)Bu, with trifluoroaceticacid and mercuric acetate, in an inert solvent, such as toluene, and ata temperature at about room temperature, followed by treatment withhydrogen sulfide;

[0414] (iv) reaction of the resulting compounds of formula (I) in whichR¹ is aryl or heteroaryl substituted by —SH, with chlorine in aqueousacetic acid at a temperature at about room temperature;

[0415] (v) reaction of the resulting compounds of formula (I) in whichR¹ is aryl or heteroaryl substituted by —SO₂Cl, with an amine of formulaHNY¹Y².

[0416] As another example of the interconversion process, compounds offormula (I) in which R¹ is aryl or heteroaryl substituted by aryl (orheteroaryl) may be prepared by treating compounds of formula (I) inwhich R¹ is aryl or heteroaryl substituted by hydroxy withN-phenyltrifluoromethanesulfonimide as described hereinabove followed byreaction of the resulting triflate with an aryl (or heteroaryl) boronicacid ester in the presence of a suitable catalyst (e.g. palladiumtetrakis(triphenylphosphine) and aqueous sodium bicarbonate, in an inertsolvent, such as dimethylformamide, and at a temperature at about120-150° C.

[0417] As another example of the interconversion process, compounds offormula (I) in which R¹ is aryl or heteroaryl substituted by hydroxy maybe prepared by reaction of the corresponding compounds of formula (I) inwhich R¹ is aryl or heteroaryl substituted by methoxy with a Lewis acid,such as boron tribromide, in an inert solvent, such as dichloromethaneand at a temperature from about 0° C. to about room temperature.

[0418] As another example of the interconversion process, compounds offormula (I) in which R¹ is aryl or heteroaryl substituted by —OR⁴ may beprepared by alkylation the corresponding compounds of formula (I) inwhich R¹ is aryl or heteroaryl substituted by hydroxy, with compounds offormula (VII):

R⁴—X³   (VII)

[0419] wherein R⁴ is as hereinbefore defined and X³ is a halogen,preferably bromo, atom, or a tosyl group, using standard alkylationconditions. The alkylation may for example be carried out in thepresence of a base, such as an alkali metal carbonate (e.g. potassiumcarbonate or cesium carbonate), an alkali metal alkoxide (e.g. potassiumtertiary butoxide) or alkali metal hydride (e.g. sodium hydride), indimethylformamide, or dimethyl sulfoxide, at a temperature from about 0°C. to about 100° C.

[0420] Alternatively compounds of formula (I) in which R¹ is aryl orheteroaryl substituted by —OR⁴ may be prepared by reaction of thecorresponding compounds of formula (I) in which R¹ is aryl or heteroarylsubstituted by hydroxy with the appropriate alcohol of formula (VIII):

R⁴—OH   (VIII)

[0421] wherein R⁴ is as hereinbefore defined in the presence of atriarylphosphine, such a triphenylphosphine, and a dialkylacetylenedicarboxylate, such as diisopropylacetylenedicarboxylate ordimethylacetylenedicarboxylate, in an inert solvent, such as toluene,and at a temperature at about room temperature. This procedure isparticularly suitable for the preparation of compounds of formula (I) inwhich R¹ is heteroaryl substituted by —OR⁴.

[0422] As another example of the interconversion process, compounds offormula (I) in which R¹ is aryl or heteroaryl substituted by —OR⁴, whereR⁴ is propyl substituted by hydroxy, may be prepared by reaction of thecorresponding compounds of formula (I) in which R¹ is aryl or heteroarylsubstituted by —OR⁴, where R⁴ is propenyl, with borane followed byreaction with hydrogen peroxide in the presence of sodium hydroxide.This procedure is particularly suitable for the preparation of compoundsof formula (I) in which R¹ is indolyl substituted by —OCH₂CH(CH₃)OH and—OCH₂CH₂CH₂OH.

[0423] As another example of the interconversion process, compounds offormula (I) in which R¹ is aryl or heteroaryl substituted by —OR⁴, whereR⁴ is a 1,3-dihydroxyalkylene group, may be prepared by reaction of thecorresponding compounds where R⁴ is alkenyl with osmium tetroxide in thepresence of 4-methyl-morpholine N-oxide. The reaction may convenientlybe carried out in an inert solvent, such as acetone, and at atemperature at about room temperature.

[0424] As another example of the interconversion process, compounds offormula (Ia) in which R⁹ is alkyl, alkenyl, cycloalkyl,heterocycloalkyl, or alkyl substituted by —C(═O)NY¹Y², —OR⁶, —C(═O)—OR⁷,—NY¹Y² may be prepared by alkylation of the corresponding compounds offormula (Ia) in which R⁹ is hydrogen, with the appropriate halide offormula (IX):

R⁹—X⁴   (IX)

[0425] wherein R⁹ is alkyl, alkenyl, cycloalkyl, heterocycloalkyl, oralkyl substituted by —C(═O)NY¹Y², —OR⁷, —C(═O)—OR⁵, —NY¹Y² and X⁴ is ahalogen, preferably bromine, atom, using standard alkylation conditionsfor example those described hereinbefore.

[0426] As another example of the interconversion process, compounds offormula (I) containing a —N(R⁶)—C(═O)—NY³Y⁴ group in which R⁶ and Y³ areboth hydrogen and Y⁴ is as hereinbefore defined may be prepared byreaction of the corresponding compounds of formula (I) containing anamino group with an isocyanate of formula O═C═NY⁴ in an inert solvent,such as tetrahydrofuran, and at a temperature at about room temperature.

[0427] As another example of the interconversion process, compounds offormula (I) containing sulfoxide linkages may be prepared by theoxidation of corresponding compounds containing —S— linkages. Forexample, the oxidation may conveniently be carried out by means ofreaction with a peroxyacid, e.g. 3-chloroperbenzoic acid, preferably inan inert solvent, e.g. dichloromethane, preferably at or near roomtemperature, or alternatively by means of potassium hydrogenperoxomonosulfate in a medium such as aqueous methanol, buffered toabout pH5, at temperatures between about 0° C. and room temperature.This latter method is preferred for compounds containing an acid-labilegroup.

[0428] As another example of the interconversion process, compounds offormula (I) containing sulfone linkages may be prepared by the oxidationof corresponding compounds containing —S— or sulfoxide linkages. Forexample, the oxidation may conveniently be carried out by means ofreaction with a peroxyacid, e.g. 3-chloroperbenzoic acid, preferably inan inert solvent, e.g. dichloromethane, preferably at or near roomtemperature.

[0429] As another example of the interconversion process, compounds offormula (I) containing a cyano group may be prepared by reaction of thecorresponding compounds of formula (I) containing a —C(═O)—NH₂ groupwith phosphorus pentachloride in the presence of triethylamine. Thereaction may conveniently be carried out in an inert solvent, such astetrahydrofuran, and at a temperature at about reflux temperature.

[0430] As another example of the interconversion process, compounds offormula (I) containing a tetrazolyl group may be prepared by reaction ofthe corresponding compounds of formula (I) containing a cyano group withazidotributyltin. The reaction may conveniently be carried out in aninert solvent, such as toluene, and at a temperature at about refluxtemperature.

[0431] As another example of the interconversion process, compounds offormula (I) in which R² is a fluoro may be prepared by reaction of thecorresponding compounds of formula (I) in which R² is hydrogen withmethyl magnesium bromide (in an inert solvent, such as tetrahydrofuran,and at a temperature at about 0° C.) followed by reaction with1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2,2,2]octanebis(tetrafluoroborate) at a temperature from about 0° C. to about refluxtemperature.

[0432] It will be appreciated that compounds of the present inventionmay contain asymmetric centres. These asymmetric centres mayindependently be in either the R or S configuration. It will be apparentto those skilled in the art that certain compounds of the invention mayalso exhibit geometrical isomerism. It is to be understood that thepresent invention includes individual geometrical isomers andstereoisomers and mixtures thereof, including racemic mixtures, ofcompounds of formula (I) hereinabove. Such isomers can be separated fromtheir mixtures, by the application or adaptation of known methods, forexample chromatographic techniques and recrystallisation techniques, orthey are separately prepared from the appropriate isomers of theirintermediates.

[0433] According to a further feature of the invention, acid additionsalts of the compounds of this invention may be prepared by reaction ofthe free base with the appropriate acid, by the application oradaptation of known methods. For example, the acid addition salts of thecompounds of this invention may be prepared either by dissolving thefree base in water or aqueous alcohol solution or other suitablesolvents containing the appropriate acid and isolating the salt byevaporating the solution, or by reacting the free base and acid in anorganic solvent, in which case the salt separates directly or can beobtained by concentration of the solution.

[0434] The acid addition salts of the compounds of this invention can beregenerated from the salts by the application or adaptation of knownmethods. For example, parent compounds of the invention can beregenerated from their acid addition salts by treatment with an alkali,e.g. aqueous sodium bicarbonate solution or aqueous ammonia solution.

[0435] Compounds of this invention can be regenerated from their baseaddition salts by the application or adaptation of known methods. Forexample, parent compounds of the invention can be regenerated from theirbase addition salts by treatment with an acid, e.g. hydrochloric acid.

[0436] Compounds of the present invention may be conveniently prepared,or formed during the process of the invention, as solvates (e.g.hydrates). Hydrates of compounds of the present invention may beconveniently prepared by recrystallisation from an aqueous/organicsolvent mixture, using organic solvents such as dioxan, tetrahydrofuranor methanol.

[0437] According to a further feature of the invention, base additionsalts of the compounds of this invention may be prepared by reaction ofthe free acid with the appropriate base, by the application oradaptation of known methods. For example, the base addition salts of thecompounds of this invention may be prepared either by dissolving thefree acid in water or aqueous alcohol solution or other suitablesolvents containing the appropriate base and isolating the salt byevaporating the solution, or by reacting the free acid and base in anorganic solvent, in which case the salt separates directly or can beobtained by concentration of the solution.

[0438] The starting materials and intermediates may be prepared by theapplication or adaptation of known methods, for example methods asdescribed in the Reference Examples or their obvious chemicalequivalents.

[0439] Compounds of formula (IV) wherein R¹ is as defined hereinbeforemay be prepared by reaction of the corresponding compounds of formula(1):

R¹—CHO   (1)

[0440] wherein R¹ is as hereinbefore defined, with hydroxylaminehydrochloride in an inert solvent, such as dimethylformamide, and at atemperature at about 150° C.

[0441] Compounds of formula (IV) wherein R¹ is represented by theformula (IIa), in which R¹⁰ and p are as hereinbefore defined and R⁹ isalkyl, alkenyl, cycloalkyl or alkyl substituted by —C(═O)NY¹Y², —OR⁴,—C(═O)—OR⁷, —NY¹Y², may be prepared by alkylation of the corresponding1H-indoles of formula (IV) wherein R¹ is represented by the formula(IIa), in which R¹⁰ and p are as hereinbefore defined and R⁹ ishydrogen, with the appropriate (optionally substituted)alkyl-, alkenyl-or cycloalkyl-halide using standard alkylation conditions. Thealkylation may for example be carried out in the presence of a base,such as an alkali metal carbonate, e.g. potassium carbonate, or alkalimetal hydride, e.g. sodium hydride, in an inert solvent, such asdimethylformamide or dimethyl sulfoxide, at a temperature from aboutroom temperature to about 100° C.

[0442] Compounds of formula (IV) wherein R¹ is5,6,7,8-tetrahydroindolizin-1-yl may be prepared by:

[0443] (i) reaction of piperidine-2-carboxylic acid with formic acid andacetic anhydride at a temperature at about room temperature;

[0444] (ii) treatment of the resultingsodium-1-formyl-piperidine-2-carboxylate with 4-toluenesulfonyl chloridein an inert solvent, such as dichloromethane, and at a temperature atabout room temperature;

[0445] (iii) reaction with acrylonitrile in the presence oftriethylamine at a temperature at about room temperature.

[0446] Compounds of formula (1) wherein R¹ is as defined hereinbeforemay be prepared by formylation of compounds of formula (2):

R¹—H   (2)

[0447] wherein R is as defined hereinbefore using standard reactionconditions, for example using a Vilsmeier-Haack formylation reactionwith phosphorus oxychloride in dimethylformamide. This procedure isparticularly suitable for the preparation of compounds of formula (1)where R¹ is optionally substituted N-methylindol-3-yl.

[0448] Compounds of formula (V) wherein R², R³ and X¹ are ashereinbefore defined and X² is an iodine atom, may be prepared byiodination of compounds of formula (3):

[0449] wherein R², R³ and X¹ are as hereinbefore defined. The iodinationreaction may conveniently be carried out by the application oradaptation of the procedure described by Saulnier and Gribble,J.Org.Chem., 1982, 47, 1982, for example by treatment of compounds offormula (3) with lithium diisopropylamide in an inert solvent, such astetrahydrofuran, and at a temperature at about −78° C., followed byreaction of the resulting anion with iodine. This reaction isconveniently carried out with the indole NH protected with for example atosyl group.

[0450] Compounds of formula (3) wherein R², R³ and X¹ are ashereinbefore defined may be prepared by cyclisation of compounds offormula (4):

[0451] wherein R², R³ and X¹ are as hereinbefore defined. Thecyclisation reaction may conveniently be carried out in the presence ofan alkali metal alkoxide, such as sodium ethoxide, in an inert solvent,such as ethanol, and at a temperature from about room temperature toabout reflux temperature.

[0452] Compounds of formula (3) wherein R³ and X¹ are as hereinbeforedefined and R² is hydrogen may be prepared by cyclisation of compoundsof formula (5):

[0453] wherein R³ and X¹ are as hereinbefore defined. The cyclisationreaction may conveniently be carried out in the presence of sodamide, inN-methylaniline and at a temperature from about 120° C. to about 200° C.

[0454] Compounds of formula (3) wherein R³ and X¹ are as hereinbeforedefined and R² is methyl (or C₁₋₄alkyl optionally substituted by —Z¹R⁸,in which Z¹ and R⁸ as hereinbefore defined) may be prepared bycyclisation of compounds of formula (6):

[0455] wherein R³ and X¹ are as hereinbefore defined, R¹¹ is hydrogen(or C₁₋₃alkyl optionally substituted by —Z¹R⁸, in which Z¹ and R⁸ ashereinbefore defined) and X⁵ represents a halogen, preferably a bromine,atom, or a triflate group. The cyclisation may conveniently be carriedout in the presence of a complex metal catalyst such astetrakis(triphenylphosphine)palladium(0), a tertiary amine, such astriethylamine, and a triarylphosphine, such as triphenylphosphine, in aninert solvent, such as dimethylformamide and at a temperature at about60° C. to about 120° C. This procedure is particularly suitable for thepreparation of compounds of formula (3) wherein R³ and X¹ are ashereinbefore defined, X¹ is N and R² is C—CH₃.

[0456] Compounds of formula (3) wherein R³, R² and X¹ are ashereinbefore defined may be prepared by:

[0457] (i) reaction of compounds of formula (7):

[0458]  wherein R³ and X¹ are as hereinbefore defined and X⁶ is ahalogen, preferably iodine, atom with acetylenes of formula (8):

R²—C≡C—SiMe₃   (8)

[0459]  wherein R² is as hereinbefore defined, in the presence of acomplex metal catalyst such as[1,1′-bis(diphenylphosphino)-ferrocene]palladium (II) chloride, lithiumchloride and sodium carbonate, in an inert solvent, such asdimethylformamide, and at a temperature up to about 100° C.

[0460] (ii) desilylation.

[0461] Compounds of formula (4) wherein R², R³ and X¹ are ashereinbefore defined may be prepared by reaction of compounds of formula(9):

[0462] wherein R², R³ and X¹ are as hereinbefore defined with a mixtureof formic acid and acetic anhydride.

[0463] Compounds of formula (5) wherein R³ and X¹ are as hereinbeforedefined may be prepared by reaction of the corresponding compounds offormula (9) wherein R³ and X¹ are as hereinbefore defined and R² ishydrogen with triethylorthoformate, in the presence of an acid catalyst,such as hydrogen chloride, in ethanol and at a temperature from aboutroom temperature to about reflux temperature.

[0464] Compounds of formula (6) wherein R³, R¹¹ and X¹ are ashereinbefore defined and X⁵ is a halogen atom may be prepared byalkylation of compounds of formula (7) wherein R³, X¹ and X⁶ are ashereinbefore defined with the appropriate alkenyl halide of formula(10):

R¹¹CH═CH—CH₂—X⁷   (10)

[0465] wherein R¹¹ is as hereinbefore defined and X⁷ is a halogen,preferably bromine, atom. The alkylation may conveniently be carried outin the presence of an alkali metal hydride, such as sodium hydride, inan inert solvent, such as tetrahydrofuran, and at a temperature at aboutroom temperature.

[0466] Compounds of formula (7) wherein R³ and X¹ are as hereinbeforedefined and X⁶ is a bromine atom, may be prepared by bromination ofcompounds of formula (11):

[0467] wherein R³ and X¹ are as hereinbefore defined, indimethylsulfoxide.

[0468] Compounds of formula (7) wherein R³ and X¹ are as hereinbeforedefined and X⁵ is an iodine atom, may be prepared by iodination ofcompounds of formula (11) wherein R³ and X¹ are as hereinbefore defined.The iodination may be carried out by the application or adaptation ofthe method of W-W. Sy, Synth.Comm., 1992, 22, pages 3215-3219.

[0469] Compounds of formula (V) wherein R¹, R², R³ and X¹ are ashereinbefore defined and X⁵ is a triflate group may be prepared byreaction of compounds of formula (12):

[0470] wherein R², R³ and X¹ are as hereinbefore defined, with triflicanhydride in the presence of Hunigs base, in an inert solvent, such asdichloromethane, and at a temperature at about 0° C. This reaction isconveniently carried out with the indole NH protected with for example atosyl group.

[0471] Compounds of formula (12) wherein R², R³ and X¹ are ashereinbefore defined may be prepared by reaction of compounds of formula(13):

[0472] wherein R³ and X¹ are as hereinbefore defined withmeta-chloroperbenzoic acid, in an inert solvent, such asdichloromethane, and at a temperature at about 5° C. This reaction isconveniently carried out with the indole NH protected with for example atosyl group.

[0473] Compounds of formula (13) wherein R³ and X¹ are as hereinbeforedefined may be prepared by reaction of compounds of formula (14):

[0474] wherein R³ and X¹ are as hereinbefore defined with lithiumdiisopropylamide, in an inert solvent, such as tetrahydrofuran, followedby reaction with dimethylformamide and at a temperature at about −78° C.This reaction is conveniently carried out with the indole NH protectedwith for example a tosyl group.

[0475] Compounds of formula (14) wherein R³ and X¹ are as hereinbeforedefined may be prepared by reaction of compounds of formula (7) whereinR³ and X¹ are as hereinbefore defined and X⁶ is iodo, withtrimethylsilylacetylene in the presence of a complex metal catalyst suchas [1,1′-bis(diphenylphosphino)-ferrocene]palladium (11) chloride,followed by desilylation.

[0476] Compounds of formula (VI) wherein R¹ is as defined hereinbeforemay be prepared by: reaction of compounds of formula (15):

R¹—X⁸   (15)

[0477] wherein R is as defined hereinbefore and X⁸ is a halogen,preferably bromine, atom, in the presence of tributylborate, with asuitable base, such as butyllithium, in an inert solvent, such astetrahydrofuran, and at a temperature at about −100° C.

[0478] Compounds of formula (VI) wherein R¹ is as defined hereinbeforemay also be prepared by treatment of compounds of formula (15), whereinR¹ is as defined hereinbefore and X⁸ is a —HgOAc group, with borane, inan inert solvent, such as tetrahydrofuran, and at a temperature at aboutroom temperature.

[0479] Compounds of formula (15) wherein R¹ is optionally substitutedindol-3-yl and X⁸ is a bromine atom may be prepared by reaction ofoptionally substituted indoles with bromine in an inert solvent, such asdimethylformamide, and at a temperature at about room temperature.

[0480] Compounds of formula (13) wherein R¹ is optionally substitutedindol-3-yl and X⁸ is a —HgOAc group may be prepared by reaction ofoptionally substituted indolines with mercuric acetate in glacial aceticacid at a temperature at about room temperature.

[0481] The present invention is further Exemplified but not limited bythe following illustrative Examples and Reference Examples.

[0482] 400M Hz ¹H nuclear magnetic resonance spectra (NMR) were recordedon a Varian Unity INOVA machine. In the nuclear magnetic resonancespectra (NMR) the chemical shifts (δ) are expressed in ppm relative totetramethylsilane. Abbreviations have the following significances:s=singlet; d=doublet; t=triplet; m=multiplet; q=quartet; dd=doublet ofdoublets; ddd=doublet of double doublets.

[0483] The high pressure liquid chromatography retention times (HPLC:R_(T) values) were determined by: (i) Method A, C18 Phenomenex (150×4.6mm) column using gradient elution with a mixture of acetonitrile andwater with 0.1% trifluoroacetic acid as the mobile phase (0-1 minute 5%acetonitrile; 1-12 minutes ramp up to 95% acetonitrile; 12-14.95 minutes95% acetonitrile; 14.95-15 minutes 0% acetonitrile); or Method B, YMCODS-AQ (2×50 mm) column using gradient elution with a mixtures ofacetonitrile and water with 0.1% formic acid as the mobile phase[95/5/0.1% (A) to 5/95/0.1% (B)] and a flow rate of 0.4 mL/minute); orMethod C, what column ?? column using gradient elution with a mixture ofacetonitrile and water with 0.1% formic acid as the mobile phase(95/5/0.1%, water/acetonitrile/formic acid for 0.1 minute lineargradient to 5/95/0.1%, water/acetonitrile/formic acid at 2 minutes andhold until 3.5 minutes).

[0484] The thin layer chromatography (TLC) R_(F) values were determinedusing Merck silica plates.

EXAMPLE 1

[0485] (a)6-(5-Methoxy-1-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine

[0486] A stirred solution of diisopropylamine (59.9 mL) intetrahydrofuran (1400 mL), at −15° C. and under nitrogen, was treatedwith a solution of n-butyllithium in hexanes (131 mL, 1.6M) over 25minutes, whilst maintaining the temperature below −10° C. After stirringfor 30 minutes the mixture was treated with methylpyrazine (26.8 g) over15 minutes, then stirred for 1 hour and then treated with a solution of5-methoxy-1-methyl-1H-indole-3-carbonitrile [53 g, Reference Example1(a)] in tetrahydrofuran (600 mL) over 1 hour, keeping the temperaturebelow −10° C. The reaction mixture was allowed to warm to roomtemperature over 2 hours, then stood overnight, then treated with water(100 mL). The tetrahydrofuran was removed in vacuo and the resultantmixture was partitioned between ethyl acetate (500 mL) and water (20mL). The two layers were separated, and the aqueous layer was extractedwith ethyl acetate (200 mL). The combined organics were washed withwater (500 mL) then evaporated. The residue was subjected to flashchromatography on silica eluting with a mixture of dichloromethane andmethanol (19:1, v/v) to give the title compound (19.4 g) as a greysolid, m.p. 270-272° C. MS: 279 (MH⁺).

[0487] (b) By proceeding in a manner similar to Example 1(a) above butusing 1-methyl-indole-3-carbonitrile [Reference Example 2(b)], there wasprepared 6-(1-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine as ayellow solid, m.p. 264-266° C. [Elemental analysis: C, 72.34; H, 4.68;N, 22.28%. Calculated for C₁₅H₁₂N₄: C, 72.56; H, 4.87; N, 22.57%].

[0488] (c) By proceeding in a manner similar to Example 1(a) above butusing 3-bromobenzonitrile, there was prepared6-(3-bromophenyl)-5H-pyrrolo[2,3-b]pyrazine as a colourless solid, m.p.247-249° C. MS: 276 (MH⁺).

[0489] (d) By proceeding in a manner similar to Example 1(a) above butusing 2-isobutylpyrazine and benzonitrile, there was prepared7-iso-propyl-6-phenyl-5H-pyrrolo[2,3-b]pyrazine as a colourless solid,m.p. 216-218° C. MS: 238 (MH⁺).

[0490] (e) By proceeding in a manner similar to Example 1(a) above butusing 4-bromobenzonitrile, there was prepared6-(4-bromophenyl)-5H-pyrrolo[2,3-b]pyrazine as a colourless solid, m.p.326-329° C. MS: 276 (MH⁺).

[0491] (f) By proceeding in a manner similar to Example 1(a) above butusing 2-(4-cyanophenyl)-1,3-dioxane (prepared as described in U.S.patent application Ser. No. 5,750,723 for example 3a), there wasprepared 6-(4-[1,3]dioxan-2-yl-phenyl)-5H-pyrrolo[2,3-b]pyrazine as ayellow solid, m.p. 288-289° C. TLC: R_(F)=0.34 (ethyl acetate/pentane:1/1).

[0492] (g) By proceeding in a manner similar to Example 1(a) above butusing 2-(3-cyanophenyl)-1,3-dioxane (prepared as described in U.S.patent application Ser. No. 5,750,723 for example 3a), there wasprepared 6-(3-[1,3]dioxan-2-yl-phenyl)-5H-pyrrolo[2,3-b]pyrazine as ayellow solid, m.p. 205-206° C. [Elemental analysis: C, 68.28; H, 5.46;N,15.02%. Calculated for C₁₆H₁₅N₃O₂: C, 68.31; H, 5.37; N, 14.94%].

[0493] (h) By proceeding in a manner similar to Example 1(a) above butusing 2-quinolinecarbonitrile, there was prepared2-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-quinoline as a pale yellow solid, m.p.293-295° C. MS: 247 (MH⁺). [Elemental analysis: C, 72.76; H, 3.82;N,22.56%. Calculated for C₁₆H₁₅N₃O₂: C, 73.16; H, 4.09; N, 22.56%].

[0494] (i) By proceeding in a manner similar to Example 1(a) above butusing 3-isoquinolinecarbonitrile, there was prepared3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-isoquinoline as a green solid, m.p.281-285° C. MS: 247 (MH⁺).

[0495] (j) By proceeding in a manner similar to Example 1(a) above butusing 1-methyl-1H-indole-5-carbonitrile [Reference Example 2(c)], therewas prepared 6-[1-methyl-1H-indol-5-yl]-5H-pyrrolo[2,3-b]pyrazine as ayellow solid, m.p. 260-265° C. MS: 249 (MH⁺).

[0496] (k) By proceeding in a manner similar to Example 1(a) above butusing 2-6-dimethylpyrazine, there was prepared6-(5-methoxy-1-methyl-1H-indol-3-yl)-2-methyl-5H-pyrrolo[2,3-b]pyrazineas a yellow solid, MS: 293 (MH⁺). ¹H NMR [(CD₃)₂SO]: δ 12.2-12.3 (1H,broad s); 8.54, 8.56 (each 1H, s); 7.50 (1H, d, J=8.9 Hz); 7.47 (1H, d,J=2.4 Hz); 6.96 (1H, dd, J=8.9 and 2.4 Hz); 6.91 (1H, s); 3.91, 3.87 and2.57(each 3H, s).

[0497] (l) By proceeding in a manner similar to Example 1(a) above butusing 2,5-dimethylpyrazine and 1-methyl-1H-indole-3-carbonitrile[Reference Example 2(c)], there was prepared3-methyl-6-(1-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine as ayellow solid, m.p. 170-175° C. MS: 263 (MH⁺).

[0498] (m) By proceeding in a manner similar to Example 1(a) above butusing 1-benzyl-5-methoxy-1H-indole-3-carbonitrile [Reference Example2(g)], there was prepared6-(1-benzyl-5-methoxy-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine as ayellow solid, m.p. 240-244° C. TLC: R_(F)=0.5 (dichloromethane/methanol:19/1).

[0499] (n) By proceeding in a manner similar to Example 1(a) above butusing 1-methyl-1H-pyrrole-3-carbonitrile [Reference Example 2(i)], therewas prepared 6-(1-methyl-1H-pyrrol-3-yl)-5H-pyrrolo[2,3-b]pyrazine as ayellow solid, m.p. 211-213° C. MS: 199 (MH⁺).

[0500] (o) By proceeding in a manner similar to Example 1(a) above butusing 1-methyl-1H-pyrrole-2-carbonitrile [Reference Example 2(j)], therewas prepared 6-(1-methyl-1H-pyrrol-2-yl)-5H-pyrrolo[2,3-b]pyrazine as ayellow solid, m.p. 208-209° C. MS: 199 (MH⁺).

[0501] (p) By proceeding in a manner similar to Example 1(a) above butusing indolizine-1-carbonitrile [Reference Example 5], there wasprepared 6-indolizin-1-yl-5H-pyrrolo[2,3-b]pyrazine as a yellow solid,m.p. 224-225° C. (with decomposition). MS: 235 (MH⁺).

[0502] (q) By proceeding in a manner similar to Example 1(a) above butusing 3-methyl-indolizine-1-carbonitrile [Reference Example 6], therewas prepared 6-(3-methyl-indolizin-1-yl)-5H-pyrrolo[2,3-b]pyrazine as ayellow solid, m.p. 233-235° C. (with decomposition). MS: 249 (MH⁺).

[0503] (r) By proceeding in a manner similar to Example 1(a) above butusing 1-methyl-5-phenyl-1H-pyrrole-3-carbonitrile [Reference Example2(k)], there was prepared6-(1-methyl-5-phenyl-1H-pyrrol-3-yl)-5H-pyrrolo[2,3-b]pyrazine as ayellow solid, m.p. 221-222° C. (with decomposition). MS: 275 (MH⁺).

[0504] (s) By proceeding in a manner similar to Example 1(a) above butusing 5,6,7,8-tetrahydroindolizine-1-carbonitrile [Reference Example 8],there was prepared6-(5,6,7,8-tetrahydroindolizin-1yl)-5H-pyrrolo[2,3-b]pyrazine as ayellow solid, m.p. 236-238° C. (with decomposition). MS: 239 (MH⁺).

[0505] (t) By proceeding in a manner similar to Example 1(a) above butusing 3-furonitrile there was prepared6-furan-3-yl-5H-pyrrolo[2,3-b]pyrazine as an orange solid. MS: 186.79(MH⁺). TLC: R_(F)=0.45 (dichloromethane/methanol: 19/1).

[0506] (u) By proceeding in a manner similar to Example 1(a) above butusing 4-N,N-dimethylaminobenzonitrile, there was prepareddimethyl-[4-(5H-pyrrolo[2,3-b]pyrazin-6-yl)phenyl]-amine as a yellowsolid, m.p. 297-298° C. MS: 239 (MH⁺).

[0507] (v) By proceeding in a similar manner to Example 1(a) but usingethylpyrazine there was prepared6-(5-methoxy-1-methyl-1H-indol-3-yl)-7-methyl-5H-pyrrolo[2,3-b]pyrazineas a yellow solid, m.p. 243-244° C. HPLC (METHOD A): R_(T)=6.73 minutes.

[0508] (w) By proceeding in a manner similar to Example 1 (a) above butusing 4-tert-butylbenzonitrile, there was prepared6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazine as a yellow solid.LCMS: R_(T)=3.29 minutes; 252 (MH⁺).

[0509] (x) By proceeding in a manner similar to Example 1 (a) above butusing 2-ethylpyrazine and 4-tert-butylbenzonitrile, there was prepared6-(4-tert-butylphenyl)-7-methyl-5H-pyrrolo[2,3-b]pyrazine as a yellowsolid, m.p. 213-214° C. MS: 266(MH⁺).

[0510] (y) By proceeding in a manner similar to Example 1 (a) above butusing 3,4-dimethoxybenzonitrile, there was prepared6-(3,4-dimethoxyphenyl)-5H-pyrrolo[2,3-b]pyrazine as a yellow/orangesolid, m.p. 212-214° C. MS: 256 (MH⁺).

[0511] (z) By proceeding in a manner similar to Example 1 (a) above butusing 2-ethylpyrazine and 4-aminobenzonitrile, there was prepared6-(4-aminophenyl)-7-methyl-5H-pyrrolo[2,3-b]pyrazine as a brown solid,m.p. 330-332° C. MS: 225 (MH⁺).

[0512] (aa) By proceeding in a manner similar to Example 1(a) above butusing 4-(1-methyl)ethoxybenzonitrile [Reference Example 51], there wasprepared 6-[4-(1-methyl)ethoxyphenyl]-5H-pyrrolo[2,3-b]pyrazine as ayellow solid. MS: 254 (MH⁺). HPLC (METHOD B): R_(T)=1.64 minute.

[0513] (ab) By proceeding in a manner similar to Example 1(a) above butusing 1H-5-cyano-1-methyl-2-methylthioimidazole [Reference Example 52],there was prepared6-(1H-1-methyl-2-(methylthio)imidazol-5-yl)-5H-pyrrolo[2,3-b]pyrazine asa yellow solid, m.p. 230° C. MS: 246(MH⁺).

[0514] (ac) By proceeding in a manner similar to Example 1 (a) above butusing 3-cyano-1-methyl-1H-indazole [Reference Example 56(a)], there wasprepared 6-(1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine as ayellow solid. MS: 250(MH⁺), 248 (MH⁻). ¹H NMR [(CD₃)₂SO]: δ 12.5-12.6(1H, broad s); 8.38 (1H, d, J=2.4 Hz); 8.24 (d, 1H, J=7.9 Hz); 8.21 (s,1H, J=2.4 Hz); 7.76 (d, 1H, J=8.1 Hz); 7.48 (t, 1H); 7.32 (t, 1H); 7.29(s, 1H); 4.18 (s, 3H).

[0515] (ad) By proceeding in a manner similar to Example 1 (a) above butusing 3-cyano-1-methyl-4-phenyl-1H-pyrrole [Reference Example 56(b)],there was prepared6-(1-methyl-4-phenyl-1H-pyrrol-3-yl)-5H-pyrrolo[2,3-b]pyrazine as asolid, m.p. 195° C. (with decomposition). MS: 275 (MH⁺).

[0516] (ae) By proceeding in a manner similar to Example 1 (a) above butusing 4-fluorobenzonitrile, there was prepared6-(4-fluorophenyl)-5H-pyrrolo[2,3-b]pyrazine as an off-white solid. ¹HNMR [(CD₃)₂SO]: δ 12.3 (s, 1H) 8.4 (d, 1H), 8.2 (d, 1H), 8.05 (d, 2H),7.4 (d, 2H), 7.2 (s, 1H). MS: 213(MH⁺).

[0517] (af) By proceeding in a manner similar to Example 1 (a) above butusing 4-methoxybenzonitrile, there was prepared6-(4-methoxyphenyl)-5H-pyrrolo[2,3-b]pyrazine as an off-white solid,m.p. 244-246° C. MS: 225 (MH⁺).

[0518] (ag) By proceeding in a manner similar to Example 1 (a) above butusing 4-(tertiary-butyl)benzonitrile and 4-(pyrazinyl)-1-butene[Reference Example 59] there was prepared6-[4-(tert-butyl)phenyl]-7-(propenyl)-5H-pyrrolo[2,3-b]pyrazine as ayellow solid, m.p. 207-208° C. MS: 292 (MH⁺).

[0519] (ah) By proceeding in a manner similar to Example 1 (a) above butusing 4-(methylthio)benzonitrile there was prepared6-(4-methylthiophenyl)-5H-pyrrolo[2,3-b]pyrazine as a yellow solid. MS:242 (MH⁺). ¹H NMR [(CD₃)₂SO]: δ 12.48 (1H, s); 8.37 (1H, s); 8.18 (1H,s); 7.98 (2H, d, J=7.9 Hz); 7.19 (2H, d, J=7.9 Hz); 7.11 (1H, s); 2.52(3H, s).

[0520] (ai) By proceeding in a manner similar to Example 1 (a) above butusing 3-methoxybenzonitrile there was prepared6-(3-methoxylphenyl)-5H-pyrrolo[2,3-b]pyrazine as an orange solid, m.p.194-196° C. MS: 226 (MH⁺).

[0521] (aj) By proceeding in a manner similar to Example 1 (a) above butusing 1-methyl-4-cyanopyrazole (prepared according to the proceduredescribed by Yoshida in J.Het.Chem., 1995, 32, page701) there wasprepared 6-(1-methyl-1H-pyrazol-4-yl)-5H-pyrrolo[2,3-b]pyrazine as anorange solid, m.p. 232-234° C. MS: 200(MH⁺).

[0522] (ak) By proceeding in a manner similar to Example 1 (a) above butusing 1-methyl-3-cyano-5-phenylpyrazole [Reference Example 1(k)] therewas 6-(1-methyl-5-phenyl-1H-pyrazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine asan orange solid, m.p. 222-223° C. HPLC R_(T)=7.36 minutes.

[0523] (al) By proceeding in a manner similar to Example 1 (a) above butusing 2-cyano-pyridine there was prepared6-(pyridin-2-yl)-5H-pyrrolo[2,3-b]pyrazine as a yellow solid, m.p.234-235° C. ¹H NMR [(CD₃)₂SO]: δ 8.71 (1H, d, J=4.1 Hz); 8.38 (1H, s);8.24 (1H, s); 8.17 (1H, d, J=8.2 Hz); 7.93 (1H, t, J=8.2 Hz); 7.41(1H,m); 7.36 (1H, s).

[0524] (am) By proceeding in a manner similar to Example 1 (a) above butusing 4-cyano-pyridine there was prepared6-(pyridin-4-yl)-5H-pyrrolo[2,3-b]pyrazine as a yellow solid, m.p.324-326° C. ¹H NMR [(CD₃)₂SO]: δ 8.69 (2H, d, J=7.1 Hz); 8.45 (1H, s);8.33 (1H, s); 8.00 (2H, d, J=7.1 Hz); 7.47 (1H, s).

EXAMPLE 2

[0525] (a) 3-[3-(5H-Pyrrolo[2,3-b]pyrazin-6-yl)-indol-1-yl]-propan-1-ol

[0526] A solution of6-{1-[3-(tert-butyl-dimethyl-silanyloxy)-propyl]-1H-indol-3-yl}-5H-pyrrolo[2,3-b]pyrazine[29 g, Reference Example 3(a)] in tetrahydrofuran (500 mL) undernitrogen was treated with a solution of tetrabutylammonium fluoride intetrahydrofuran (144 mL, 1.0M).

[0527] After stirring at ambient temperature for 4 hours the reactionmixture was concentrated in vacuo. The residue was treated with water togive a solid which was filtered then washed with water and then dried togive the title compound (17.5 g) as a yellow-brown solid, m.p. 220-221°C. MS: 293 (MH⁺).

[0528] (b) By proceeding in a manner similar to Example 2(a) above butusing6-{1-[3-(tert-butyl-dimethyl-silanyloxy)-propyl]-5-methoxy-1H-indol-3-yl}-5H-pyrrolo[2,3-b]pyrazine[Reference Example 3(b)], there was prepared3-[5-methoxy-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-indol-1-yl]-propan-1-olas a yellow solid, m.p. 225-228° C. MS: 323 (MH⁺). TLC: R_(F)=0.16(dichloromethane/methanol: 19/1).

[0529] (c) By proceeding in a manner similar to Example 2(a) above butusing6-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-indol-3-yl}-5H-pyrrolo[2,3-b]pyrazine[Reference Example 3(c)], there was prepared2-[3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-indol-1-yl]-ethanol as a yellowsolid, m.p. 272-273° C. MS: 279 (MH⁺).

[0530] (d) By proceeding in a manner similar to Example 2(a) above butusing6-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-5-methoxy-1H-indol-3-yl]-5H-pyrrolo[2,3-bpyrazine [Reference Example 3(d)], there was prepared2-[5-methoxy-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-indol-1-yl]-ethanol as agrey solid, m.p. 270-273° C. MS: 309.43 (MH⁺).

EXAMPLE 3

[0531] (a) 3-[3-(5H-Pyrrolo[2,3-b]pyrazin-6-yl)-indol-1-yl]-propylamine

[0532] A solution of3-[3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-indol-1-yl]-propan-1-ol [12 g,Example 2(a)] and carbon tetrabromide (19.1 g) in dichloromethane (300mL) at ambient temperature was treated with a solution oftriphenylphosphine (12.9 g) in dichloromethane (100 mL) over 5 minutes.After stirring at ambient temperature for 3 hour the reaction mixturewas filtered and the solid was washed with sparing amounts ofdichloromethane. The filtrate and washings were evaporated to yield abrown gum, which was mixed with liquid ammonia (ca 80 mL) in a sealedpressure vessel and allowed to stir at ambient temperature for 18 hours.The vessel was then cooled to −78° C. and then cautiously vented. Theammonia was allowed to evaporate and the residue was subjected to flashchromatography on silica eluting with a mixture of dichloromethane,methanol and concentrated ammonia (900:100:7, v/v/v) to give the titlecompound as a yellow solid (3 g), m.p. 170° C. ¹H NMR [(CD₃)₂SO]: δ 8.28(1H, d, J=2.7 Hz); 8.18 (1H, s); 8.10, 7.64 (each 1H, d, J=7.7 Hz); 8.09(1H, d, J=2.7 Hz); 7.29, 7.23 (each 1H, td, J=7.1 and 1.0 Hz); 6.97 (1H,s); 4.32 (2H, t, J=7.0 Hz); 2.57 (2H, t, J=6.5 Hz); 1.89 (2H, quintet,J=6.4 Hz).

[0533] (b) By proceeding in a manner similar to Example 3(a) above butusing3-[5-methoxy-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-indol-1-yl]-propan-1-ol[Example 2(b)], there was prepared3-[5-methoxy-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-indol-1-yl]-propylamineas a yellow solid, m.p. 95-100° C. and 150-160° C. MS: 322 (MH⁺). TLC:R_(F)=0.2 (dichloromethane/methanol/concentrated ammonia: 900/100/7,v/v/v).

EXAMPLE 4

[0534]N-{3-[3-(5H-Pyrrolo[2,3-b]pyrazin-6-yl)-indol-1-yl]-propyl}-acetamide

[0535] Acetyl chloride (31 μl) was added dropwise to a solution of3-[3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-indol-1-yl]-propylamine [100 mg,Example 3(a)] and triethylamine (52.2 μl) and dichloromethane (20 mL) atambient temperature under a nitrogen atmosphere. After stirring for 24hours at ambient temperature the reaction mixture was evaporated. Theresidue was subjected to flash chromatography on silica eluting with amixture of dichloromethane and methanol (9:1, v/v) to give the titlecompound (82 mg) as a yellow solid, m.p. 260° C. MS: 334 (MH⁺).

EXAMPLE 5

[0536] (a)6-[1-(3-Morpholin-4-yl-propyl)-1H-indol-3-yl]-5H-pyrrolo[2,3-b]pyrazine

[0537] A mixture of3-[3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-indol-1-yl]-propylbromide [250 mg,Reference Example 4], morpholine (0.5 mL), potassium carbonate (100 mg)and potassium iodide (2 crystals) in ethyl methyl ketone was heated atreflux for 2 hours. The mixture was then allowed to cool to ambienttemperature over 16 hours then evaporated. The residue was subjected toflash chromatography on silica eluting with a mixture of dichloromethaneand methanol (9:1, v/v) to give a yellow glass which was triturated withethyl acetate and pentane to give the title compound (40 mg) as a yellowsolid, m.p. 180-185° C. MS: 362 (MH⁺).

[0538] (b) By proceeding in a manner similar to Example 5(a) above butusing piperidine, there was prepared6-[1-(3-piperidin-1-yl-propyl)-1H-indol-3-yl]-5H-pyrrolo[2,3-b]pyrazineas a yellow solid, m.p. 240° C. MS: 360 (MH⁺).

EXAMPLE 6

[0539]6-{1-[3-(Pyridin-3-yloxy)-propyl]-1H-indol-3-yl}-5H-pyrrolo[2,3-b]pyrazine

[0540] A solution of diisopropylazodicarboxylate (269 μM) intetrahydrofuran (0.5 mL) was added dropwise, over 2 minutes, to asolution of triphenylphosphine (359 mg) in tetrahydrofuran (2.5 mL) at0° C. under an atmosphere of nitrogen. After stirring at thattemperature for 20 minutes the mixture was treated with a solution of3-hydroxypyridine (65 mg) in tetrahydrofuran (1 mL) over 1 minute thenwith a suspension of3-[3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-indol-1-yl]-propan-1-ol [200 mg,Example 2(a)] in tetrahydrofuran (2 mL). The mixture was allowed to warmto ambient temperature over 18 hours then evaporated. The residue wassubjected to flash chromatography on silica eluting with a mixture ofethyl acetate and methanol (9:1, v/v) to give the title compound (110mg) as a yellow solid, m.p. 208-209° C. MS: 370 (MH⁺).

EXAMPLE 7

[0541] 1-Methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indol-5-ol

[0542] A mixture of6-(5-methoxy-1-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine [200 mg,Example 1(a)] hydrobromic acid (48%, 500 μl) and glacial acetic acid (3mL) was heated under reflux for 14 hours. After cooling the mixture wasneutralised by addition of saturated sodium bicarbonate solution. Theresulting dark solid was filtered and then dried to give the titlecompound (180 mg) as a black solid, m.p. 289-290° C. MS: 264 (MH⁺).

EXAMPLE 8

[0543]6-(2-Chloro-5-methoxy-1-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine

[0544] A solution of6-(5-methoxy-1-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine [100 mg,Example 1(a)] in dimethoxy ethanol (25 mL), cooled to −78° C., wastreated with a solution of n-butyllithium in hexanes (172 μl, 2.5M).After stirring for 30 minutes the mixture was treated with4-toluenesulfonyl chloride (82 mg) then allowed to warm slowly toambient temperature and then evaporated. The residue was subjected toflash chromatography on silica eluting with a mixture of dichloromethaneand methanol (19:1, v/v) to give the title compound (45 mg) as a blacksolid. MS: 313 (MH⁺). ¹H NMR [(CD₃)₂SO]: δ 12.20 (1H, s); 8.39 (1H, d,J=3 Hz); 8.21 (1H, d, J=3 Hz); 7.54 (1H, d, J=9 Hz); 7.30 (1H, d, J=2Hz); 6.96 (1H, dd, J=9 and 2 Hz); 6.84 (1H, d, J=2 Hz); 3.82 (3H, s);3.81 (3H, s).

EXAMPLE 9

[0545] (a) 3-(5H-Pyrrolo[2,3-b]pyrazin-6-yl)-benzaldehyde

[0546] A solution of6-(3-[1,3]dioxan-2-yl-phenyl)-5H-pyrrolo[2,3-b]pyrazine [1.6 g, Example1(g)] in dichloromethane (50 mL) was treated with trifluoroacetic acid(5 mL). The resultant mixture was heated at reflux for 6 hours, thenallowed to cool overnight and then evaporated. The residue wastriturated with diethyl ether to give a yellow solid which wasrecrystallised from ethyl acetate to give the title compound (0.6 g) asa yellow crystalline solid, m.p. 268-270° C. [Elemental analysis: C,69.96; H, 3.92; N,18.69%. Calculated for C₁₃H₉N₃O: C, 69.95; H, 4.06; N,18.82%].

[0547] (b) By proceeding in a manner similar to Example 9(a) above butusing 6-(4-[1,3]dioxan-2-ylphenyl)-5H-pyrrolo[2,3-b]pyrazine [Example1(f)], there was prepared 4-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-benzaldehydehydrate as a yellow solid, m.p. >295° C. [Elemental analysis: C, 67.57;H, 4.33; N,18.04%. Calculated for C₁₃H₉N₃O.H₂O: C, 67.23; H, 4.34; N,18.09%].

EXAMPLE 10

[0548] (a) [3-(5H-Pyrrolo[2,3-b]pyrazin-6-yl)-phenyl]-methanol

[0549] A suspension of 3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-benzaldehyde[0.4 g, Example 9(a)] in ethanol (50 mL) was treated with sodiumborohydride (200 mg). The mixture was allowed to stir at ambienttemperature for 1 hour then treated with water (10 mL) and thenevaporated. The residual solid was triturated with water (50 mL) to givea pale yellow solid which was washed with water and then recrystallisedfrom methanol to yield the title compound (0.35 g) as a yellowcrystalline solid, m.p. 225-226° C. [Elemental analysis: C, 68.72; H,4.73; N,18.44%. Calculated for C₁₃H₁₁N₃O: C, 69.32; H, 4.92; N, 18.65%].

[0550] (b) By proceeding in a manner similar to Example 10(a) above butusing 4-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-benzaldehyde [Example 9(b)],there was prepared [4-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-phenyl]-methanolas a yellow solid, m.p. 284-285° C. [Elemental analysis: C, 68.61; H,4.65; N,18.28. Calculated for C₁₃H₁₁N₃O: C, 69.32; H, 4.92; N, 18.65%].

EXAMPLE 11

[0551] 6-(5-Methoxy-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine

[0552] A cooled (−78° C.) solution of6-(1-benzyl-5-methoxy-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine [50 mg,Example 1(m)] in tetrahydrofuran (20 mL) was treated with liquid ammonia(20 mL) then with sodium (100 mg). After stirring at −78° C. for 30minutes the reaction mixture was allowed to warm slowly to ambienttemperature, then treated with water (50 mL) and then extracted threetimes with ethyl acetate (50 mL). The combined extracts were dried oversodium sulfate and then evaporated. The residue was triturated withdiethyl ether to give the title compound (14 mg) as a brown solid, m.p.268-271° C. MS: 265.24 (MH⁺).

EXAMPLE 12

[0553]2-[5-Methoxy-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-indol-1-yl]-1-morpholin-4-yl-ethanone

[0554] A stirred solution of6-(5-methoxy-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine [70 mg, Example11] in dry dimethylformamide (10 mL) was treated with sodium hydride(21.6 mg, 60% dispersion in mineral oil). After stirring for 30 minutesthis mixture was treated with a solution of 4-(2-chloroacetyl)morpholine(44.1 mg) in dimethylformamide (1 mL) and stirring was continued for afurther 3 hours. The reaction mixture was poured into water (20 mL) andthen extracted three times with ethyl acetate (30 mL). The combinedextracts were dried over sodium sulfate and then evaporated. The residuewas triturated with diethyl ether to give the title compound (55 mg) asa yellow solid, m.p. 263-267° C. MS: 392.21 (MH⁺).

EXAMPLE 13

[0555] (a)[5-Methoxy-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-indol-1-yl]-acetic Acid

[0556] A mixture of{5-methoxy-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-indol-1-yl}-aceticacid ethyl ester [4.67 g, Reference Example 13(a)], methanol (250 mL)and aqueous potassium hydroxide (5M, 25 mL) were heated under reflux for7 hours. The methanol was removed under reduced pressure and the residuewas treated with water (20 mL) and the pH of this solution was adjustedto 7 by addition of concentrated hydrochloric acid. The resulting yellowsolid was filtered and subjected to flash chromatography on silicaeluting with a mixture of ethyl acetate and methanol (7:3, v/v) to givethe title compound (1.69 g) as a white solid. MS: 320 (M-H⁺). HPLC(METHOD A): R_(T)=6.67 minutes.

[0557] (b) By proceeding in a similar manner to Example 13(a) but using4-methoxy-2-(5-methoxy-1-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[Reference Example 2(l)] there was prepared4-methoxy-2-(5-methoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridineas a tan solid, m.p. 288-289° C. MS: 307(MH⁺).

[0558] (c) By proceeding in a similar manner to Example 13(a) but using4-methoxy-2-(5-methoxy-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine(Reference Example 39) there was prepared4-methoxy-2-(5-methoxy-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridine as a tansolid, m.p. 294-295° C. MS: 294(MH⁺).

[0559] (d) By proceeding in a similar manner to Example 13(a) but using4-chloro-2-(4-tertiary-butylphenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[Reference Example 12(j)] there was prepared4-chloro-2-(4-tertiary-butylphenyl)-1H-pyrrolo[2,3-b]pyridine as a creamcoloured solid. TLC: R_(F)=0.71 (ethyl acetate/heptane 1:1). ¹H NMR[(CD₃)₂SO]: δ 12.52 (1H, s); 8.16 (1H, d, J=6.1 Hz); 7.93 (2H, d, J=8.1Hz); 7.50 (2H, d, J=8.1 Hz); 7.21 (1H, d, J=6.1 Hz); 6.96 (1H, s); 1.30(9H, s).

[0560] (e) By proceeding in a similar manner to Example 13(a) but using2-(5-methoxy-1-methyl-1H-indol-3-yl)-5-phenyl-1-(toluene-4-sulfonyl)1H-pyrrolo[2,3-b]pyridineReference Example 13(j)] there was prepared2-(5-methoxy-1-methyl-1H-indol-3-yl)-5-phenyl-1H-pyrrolo[2,3-b]pyridineas a cream coloured solid, m.p. 240-242° C. MS: 354 (MH⁺).

EXAMPLE 14

[0561] (a)2-{[5-Methoxy-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-indol-1-yl]-1-morpholin-4-yl}-ethanone

[0562] A suspension of[5-methoxy-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-indol-1-yl]-acetic acid [60mg, Example 13(a)] in dry dimethylformamide (7 mL) was treated withN-{(dimethylamino)(1H-1, 2, 3, -triazolo [4,5,-b]pyridin-1-yl)methylene}-N-methylmethanaminium hexafluorophosphateN-oxide (71 mg) and diisopropylethylamine (45 μl). After stirring atroom temperature for 30 minutes morpholine (18 μl) was added and themixture stirred at ambient temperature for a further 12 hours. Thesolvent was removed in vacuo and the residue was suspended in saturatedsodium bicarbonate solution. The precipitated solid was filtered thendried to give the title compound (10 mg) as a violet coloured solid,m.p. 243-247° C. MS: 391 (MH⁺).

[0563] (b) By proceeding in a manner similar to Example 14(a) above butusing1-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yloxy]-cyclobutanecarboxylicacid [Example 15 (c)] and ammonium chloride, there was prepared1-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yloxy]-cyclobutanecarboxylicacid amide as a pale lilac solid, m.p. 267-268° C. MS: 361 (MH⁺).

[0564] (c) By proceeding in a manner similar to Example 14(a) above butusing1-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yloxy]-cyclobutanecarboxylicacid [Example 15 (c)] and methylamine, there was prepared1-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yloxy]-cyclobutanecarboxylicacid methylamide as a pale lilac solid, m.p. 249-250° C. MS: 375 (MH⁺).

[0565] (d) By proceeding in a manner similar to Example 14(a) above butusing 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylicacid [Example 15 (d)] and methylamine, there was prepared1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylic acidmethylamide as a pale orange solid, m.p. 186° C. MS: 304 (MH⁺).

[0566] (e) By proceeding in a manner similar to Example 14(a) above butusing 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylicacid [Example 15 (d)] and ethanolamine, there was prepared1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylic acid(2-hydroxy-ethyl)-amide as a yellow solid, m.p. 256-257° C. MS: 335(MH⁺).

[0567] (f) By proceeding in a manner similar to Example 14(a) above butusing 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylicacid [Example 15 (d)] and 2-aminoethyl morpholine, there was prepared1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylic acid(2-morpholin-4-yl-ethyl)-amide as a colourless solid, m.p. 268-270° C.MS: 404 (MH⁺).

[0568] (g) By proceeding in a manner similar to Example 14(a) above butusing 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylicacid [Example 15 (d)] and β-alanine-amide, there was prepared1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylic acid(2-carbamoyl-ethyl)-amide as a colourless solid, m.p. 286-288° C. MS:362 (MH⁺).

[0569] (h) By proceeding in a manner similar to Example 14(a) above butusing 1-methyl-3-(1H pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylicacid [Example 15 (d)] and diethanolamine, there was prepared1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5carboxylic acidbis-(2-hydroxy-ethyl)-amide as a yellow solid, m.p. 230-232° C. MS: 379(MH⁺).

[0570] (i) By proceeding in a manner similar to Example 14(a) above butusing 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylicacid [Example 15 (d)] and ammonium chloride, there was prepared1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)1H-indole-5-carboxylic acidamide as a yellow solid, m.p. 330-332° C. MS: 291 (MH⁺).

[0571] (j) By proceeding in a manner similar to Example 14(a) above butusing 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylicacid [Example 15 (d)] and tris(hydroxymethyl) aminomethane, there wasprepared1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylic acid(2-hydroxy-1,1-bis-hydroxymethyl-ethyl))amide as a yellow solid, m.p.205-206° C. MS: 395 (MH⁺).

[0572] (k) By proceeding in a manner similar to Example 14(a) above butusing 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylicacid [Example 15 (d)] and 2-amino-2-methyl-1,3-propanediol, there wasprepared1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylic acid(2-hydroxy-1-hydroxymethyl-1-methyl-ethyl)-amide as a yellow solid, m.p.180-182° C. MS: 379 (MH⁺).

[0573] (l) By proceeding in a manner similar to Example 14(a) above butusing 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylicacid [Example 15 (d)] and 3-amino-1,2-propanediol, there was prepared1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylic acid(2,3-dihydroxy-propyl)-amide as a yellow solid, m.p. 171-172° C. MS: 365(MH⁺).

[0574] (m) By proceeding in a manner similar to Example 14(a) above butusing 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylicacid [Example 15 (d)] and 2-amino2-methyl-1-propanol, there was prepared1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylic acid(2-hydroxy-1,1-dimethyl-ethyl)-amide as a yellow solid, m.p. 161-162° C.MS: 365 (MH⁺).

[0575] (n) By proceeding in a manner similar to Example 14(a) above butusing 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylicacid [Example 15 (d)] and serinol, there was prepared1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylic acid(2-hydroxy-1-hydroxymethyl-ethyl)-amide as a yellow solid, m.p. 178-179°C. MS: 365.41 (MH⁺).

[0576] (o) By proceeding in a manner similar to Example 14(a) above butusing 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-6-carboxylicacid [Example 15(g)] and 3-aminopropionamide hydrochloride, there wasprepared1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-6-carboxylic acid(2-carbamoyl-ethyl)-amide as a pale yellow solid, m.p. 277-280° C. MS:362 (MH⁺).

[0577] (p) By proceeding in a manner similar to Example 14(a) above butusing 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-6-carboxylicacid [Example 15(g)] and ethanolamine, there was prepared1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-6-carboxylic acid(2-hydroxy-ethyl)-amide as a brown solid, m.p. 264-267° C. MS: 335(MH⁺).

[0578] (q) By proceeding in a manner similar to Example 14(a) above butusing 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-6-carboxylicacid [Example 15(g)] and 1H-[1,2,4]triazol-3-ylamine, there was prepared1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-6-carboxylic acid(1H-[1,2,4]triazol-3-yl)-amide as a yellow solid, m.p. 343-345° C. MS:358 (MH⁺).

[0579] (r) By proceeding in a manner similar to Example 14(a) above butusing 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-6-carboxylicacid [Example 15(g)] and serinol, there was prepared1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-6-carboxylic acid(2-hydroxy-1-hydroxymethyl-ethyl)-amide as a light brown solid, m.p.247-249° C. MS: 365 (MH⁺).

[0580] (s) By proceeding in a similar manner to Example 14(a) but using1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylic acid[Example 15(i)] and 2-amino-2-methyl]-propanol there was prepared1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylic acid(2-hydroxy-1,1-dimethyl-ethyl)-amide as a yellow solid, m.p. 210-214° C.MS: 364(MH⁺).

[0581] (t) By proceeding in a manner similar to Example 14(a) above butusing 3-[6-(4-tert-butylphenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propionicacid [Example 25(a)] and methylamine, there was prepared3-[6-(4-tert-butylphenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl]-N-methylpropionamideas an off-white solid, m.p. 222-228° C. MS: 337 (MH⁺).

[0582] (u) By proceeding in a manner similar to Example 14(a) above butusing 3-[6-(4-tert-butylphenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propionicacid [Example 25(a)] and dimethylamine, there was prepared3-[6-(4-tert-butylphenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl]-N,N-dimethylpropionamideas an off-white solid, m.p. 203-204° C. MS: 351 (MH⁺).

[0583] (v) By proceeding in a manner similar to Example 14 (a) above butusing 1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylicacid [Example 15(i)] and 2-methoxyethylamine, there was prepared1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylic acid2-methoxyethylamide as an orange solid, MS: 350(MH⁺). HPLC (Method C):R_(T)=1.27 minutes.

[0584] (w) By proceeding in a manner similar to Example 14 (a) above butusing ing1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylic acid[Example 15(i)] and 2-thien-2-ylethylamine, there was prepared1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylic acid2-thien-2-ylethylamide as a yellow solid. MS: 402(MH⁺). HPLC (Method C):R_(T)=1.45 minutes.

[0585] (x) By proceeding in a manner similar to Example 14 (a) above butusing 1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylicacid [15(i)] and 2-fluoroethylamine, there was prepared1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylic acid2-fluoroethylamide as an orange solid. MS: 338(MH⁺). HPLC (Method C):R_(T)=1.30 minutes.

[0586] (y) By proceeding in a manner similar to Example 14 (a) above butusing 1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylicacid [Example 15(i)] and alanine ethyl ester hydrochloride, there wasprepared1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylic acid2-carboethoxyethylamide as an orange solid. MS: 392(MH⁺). HPLC (MethodC): R_(T)=1.38 minutes.

[0587] (z) By proceeding in a manner similar to Example 14 (a) above butusing 1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylicacid [Example 15(i)] and serine methyl ester hydrochloride, there wasprepared1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylic acid(hydroxymethyl)-carbomethoxy-methylamide as an orange solid. MS:394(MH⁺). HPLC (Method C): R_(T)=1.24 minutes.

[0588] (aa) By proceeding in a manner similar to Example 14 (a) abovebut using1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylic acid[Example 15(i)] and ethanolamine, there was prepared1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylic acid2-hydroxyethylamide as a yellow solid, m.p. 171-173° C. (withdecomposition). MS: 336 (MH⁺).

[0589] (ab) By proceeding in a manner similar to Example 14 (a) abovebut using1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylic acid[Example 15(i)] and methylamine, there was prepared1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylic acidmethylamide as a beige solid, MS: 304(MH⁺). NMR ¹H: ? solvent: δ 8.64(1H, broad s); 8.59 (d, 1H, J=1.0 Hz); 8.27(d, 1H, J=2.4 Hz); 8.17 (s,1H); 8.15 (d, 1H, J=2.4 Hz); 7.82(dd, 1H, J=1.0 Hz, 7.9 Hz); 7.62 (d,1H, J=7.9 Hz); 7.21 (s, 1H); 3.96 (s, 3H); 2.82 (s, 3H).

[0590] (ac) By proceeding in a manner similar to Example 14 (a) abovebut 1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylicacid [Example 15(i)] and dimethylamine, there was prepared1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylic aciddimethylamide as a yellow solid, MS: 320(MH). NMR ¹H: ? solvent: δ 8.26(d, 1H, J=2.1 Hz); 8.18 (s, 1H); 8.15 (d, 1H, J=2.1 Hz); 7.62(d, J=8.1Hz); 7.372 (dd, 1H, J=1.0 Hz, 8.1 Hz); 6.98 (s, 1H); 3.94 (s, 3H); 3.05(s, 6H).

[0591] (ad) By proceeding in a manner similar to Example 14 (a) abovebut using1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylic acid[Example 15(i)] and morpholine, there was prepared[1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indol-5-yl]morpholin-4-yl ketone as a yellow solid, MS: 362(MH⁺).

[0592] (ae) By proceeding in a manner similar to Example 14 (a) abovebut using1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylic acid[Example 15(i)] and 4-hydroxypiperidine, there was prepared4-hydroxy-[1-[1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indol-5-yl]carbonylpiperidineas a yellow solid, MS: 376(MH⁺), 398(MNa⁺).

[0593] (af) By proceeding in a manner similar to Example 14 (a) abovebut using3-[1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indol-5-yl]carbonylaminopropionicacid [Example 15(l)] and methylamine, there was prepared3-[1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indol-5-yl]carbonylaminopropionicacid methylamide as a yellow solid. MS: 377 (MH⁺). HPLC (Method C):R_(T)=1.20 minutes.

[0594] (ag) By proceeding in a manner similar to Example 14 (a) abovebut using1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylic acid[Example 15(i)] and 3-hydroxypropylamine, there was prepared1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylic acid3-hydroxypropylamide as a yellow solid. MS: 350 (MH⁺). HPLC (Method C):R_(T)=1.22 minutes.

[0595] (ah) By proceeding in a manner similar to Example 14(a) above butusing3-{6-[4-(1-methyl)ethoxyphenyl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}propionicacid [Example 25(b)] and methylamine, there was prepared3-{6-[4-(1-methyl)ethoxyphenyl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}propionicacid methylamide as a yellow solid, MS: 339 (MH⁺). HPLC (Method C):R_(T)=1.49 minutes.

[0596] (ai) By proceeding in a manner similar to Example 14(a) above butusing 3-[6-(4-methoxyphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propionicacid [Example 25(d)] and methylamine, there was prepared3-[6-(4-methoxyphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propionic acidmethylamide as an off-white solid. ¹H NMR [(CD₃)₂SO]: δ 12.0 (s, 1H) 8.3(d, 1H), 8.2 (d,1H), 7.7 (d, 2H), 7.1 (d, 2H), 3.8(s, 3H), 3.05 (t, 2H),2.6 (t, 2H) 2.5 (s, 3H). MS: 310 (MH⁺).

[0597] (aj) By proceeding in a manner similar to Example 14(a) above butusing3-{6-[4-(1-methyl)ethoxyphenyl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}propionicacid [Reference Example 25(b)] and ammonium chloride, there was prepared3-{6-[4-(1-methyl)ethoxyphenyl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}propionamideas a white solid. MS: 325 (MH⁺). HPLC (Method C): R_(T)=1.44 minutes.

[0598] (ak) By proceeding in a manner similar to Example 14(a) above butusing 3-{6-(4-hydroxyphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl}propionicacid [Example 30] and ammonium chloride, there was prepared3-[6-(4-hydroxyphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl}propionamide as awhite solid. MS: 283 (MH⁺). HPLC (Method C): R_(T)=2.18 minutes.

[0599] (al) By proceeding in a manner similar to Example 14(a) above butusing 3-[6-(4-fluorophenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propionic acid[Example 25(c)] and methylamine, there was prepared3-[6-(4-fluorophenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propionic acidmethylamide as an off-white solid. ¹H NMR [(CD₃)₂SO]: δ 12.5 (s, 1H) 8.4(d, 1H), 8.2 (d,1H), 7.8 (d, 2H), 7.4 (d, 2H), 3.1 (t, 2H), 2.6 (t, 2H),2.5 (s, 3H). MS: 298 (MH⁺).

EXAMPLE 15

[0600] (a)[1-Methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yloxy]-aceticacid

[0601] A solution of{1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-aceticacid ethyl ester [500 mg, Reference Example 15(b)] in methanol (25 mL)was treated with potassium hydroxide (5N, 3 mL) and then heated atreflux for 16 hours. The solvent was removed under reduced pressure andthe residue was treated with water (10 mL). The pH of this mixture wasadjusted to 7 by addition of acetic acid and the resulting colourlesssolid was collected by filtration then dried to give the title compound(170 mg) as a colourless solid, m.p. >300° C. MS: 322 (MH⁺).

[0602] (b) By proceeding in a manner similar to Example 15(a) above butusing3-{1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-propionicacid ethyl ester [Reference Example 15(c)], there was prepared3-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yloxy]-propionicacid as a colourless solid, m.p. 177-178° C. MS: 336 (MH⁺).

[0603] (c) By proceeding in a manner similar to Example 15(a) above butusing1-{1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-cyclobutanecarboxylicacid ethyl ester [Reference Example 15(d)], there was prepared1-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yloxy]-cyclobutanecarboxylicacid as a colourless solid, m.p. 168-169° C. MS: 362 (MH⁺).

[0604] (d) By proceeding in a manner similar to Example 15(a) above butusing1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indole-5-carboxylicacid methyl ester [Reference Example 19(a)], there was prepared1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylic acidas a yellow solid, m.p. >300° C. MS: 291 (MH⁺).

[0605] (e) By proceeding in a manner similar to Example 15(a) above butusing1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-ol[Reference Example 14(a)], there was prepared1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-ol as a yellowsolid, m.p. 199-200° C. MS: 264 (MH⁺).

[0606] (f) By proceeding in a manner similar to Example 15(a) above butusing 1-{1-(cyclobutanecarboxylic acid ethylester)-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-cyclobutanecarboxylicacid ethyl ester [Reference Example 23(d)], there was prepared1-{1-(cyclobutanecarboxylicacid)-3-[1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-cyclobutanecarboxylicacid as a yellow solid, m.p. 240 ° C. (with decomposition). MS: 444(MH⁻).

[0607] (g) By proceeding in a manner similar to Example 15(a) above butusing1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indole-6-carboxylicacid methyl ester [Reference Example 13(g)], there was prepared1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-6-carboxylic acidas a yellow solid, m.p. 359-361° C. MS 292 (MH⁺).

[0608] (h) By proceeding in a manner similar to Example 15(a) above butusing3-{1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yl}-propionicacid ethyl ester [Reference Example 38(a)], there was prepared3-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yl]-propionicacid as a yellow solid, m.p. 268-270° C. MS 320 (MH⁺).

[0609] (i) By proceeding in a similar manner to Example 15(a) but usingmethyl1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylate[Reference Example 19(b)] there was prepared1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylic acidas a brown solid, m.p. 350° C. HPLC (METHOD A):: R_(T)=5.85 minutes.

[0610] (j) By proceeding in a manner similar to Example 15 (a) above butusing [2-methoxy-5-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-phenoxy]-acetic acidethyl ester [Example 27], there was prepared[2-methoxy-5-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-phenoxy]acetic acid as awhite solid, m.p. 330-332° C. MS: 300 (MH⁺).

[0611] (k) By proceeding in a manner similar to Example 15 (a) above butusing ethyl3-[2-dimethylamino-5-(5H-pyrrolo[2,3-b]pyrazin-6-yl)phenyl]propionate[Reference Example 38(b)], there was prepared3-[2-dimethylamino-5-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-phenyl]propionicacid as an orange solid, m.p. 269-271° C. MS: 311 (MH⁺).

[0612] (l) By proceeding in a manner similar to Example 15 (a) above butusing 1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylicacid 2-carboethoxyethylamide [Example 14(y)] and sodium hydroxide, therewas prepared3-[1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indol-5-yl]carbonylaminopropionicacid as an orange solid (35 mg). MS: 364(MH⁺). HPLC (Method C):R_(T)=1.24 minutes.

EXAMPLE 16

[0613] (a)2-[1-Methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yloxy]-ethanol

[0614] A solution of{1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-aceticacid ethyl ester [120 mg, Reference Example 15(b)] in drytetrahydrofuran (5 mL) was treated with lithium aluminium hydride (1.0Msolution in tetrahydrofuran, 50 μl) at 0° C. under a nitrogenatmosphere. The mixture was allowed to warm to ambient temperature, thenstirred for 3 hours and then carefully poured into water (75 mL). Themixture was extracted three times with ethyl acetate (25 mL). Thecombined organic extracts were washed with brine (75 mL), then driedover sodium sulfate and then evaporated to give the title compound (45mg) as a colourless solid, m.p. 209-210° C. MS: 308 (MH⁺).

[0615] (b) By proceeding in a manner similar to Example 16(a) above butusing3-{1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-propionicacid ethyl ester [Reference Example 15(c)], there was prepared3-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yloxy]-propan-1-olas a colourless solid, m.p. 164-165° C. MS: 320 (MH⁺).

[0616] (c) By proceeding in a manner similar to Example 16(a) above butusing1-{1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-cyclobutanecarboxylicacid ethyl ester [Reference Example 15(d)], there was prepared{1-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yloxy]-cyclobutyl}-methanolas a colourless solid, m.p. 144-146° C. MS: 348 (MH⁺). HPLC (METHOD A):R_(T)=6.37 minutes.

[0617] (d) By proceeding in a manner similar to Example 16(a) above butusing (6-phenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl)-acetic acid [ReferenceExample 35], there was prepared2-(6-phenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl)-ethanol as a colourlesssolid, m.p. 201-202° C. MS: 348 (MH⁺). HPLC (METHOD A): R_(T)=6.37minutes. [Elemental analysis: C, 70.68; H, 5.77; N,17.44%. Calculatedfor C₁₃H₁₁N₃O: C, 70.28; H, 5.48; N, 17.56%].

[0618] (e) By proceeding in a manner similar to Example 16 (a) above butusing [2-methoxy-5-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-phenoxy]-acetic acidethyl ester [Example 27], there was prepared2-[2-methoxy-5-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-phenoxy]-ethanol as ayellow solid, m.p. 203-205° C. MS: 286 (MH⁺).

[0619] (f) By proceeding in a manner similar to Example 16 (a) above butusing ethyl3-[2-dimethylamino-5-(5H-pyrrolo[2,3-b]pyrazin-6-yl)phenyl]propionate[Reference Example 38(b)], there was prepared3-[2-dimethylamino-5-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-phenyl]-propan-1-olas a yellow solid, m.p. 203-204° C. MS: 297(MH⁺).

[0620] (g) By proceeding in a manner similar to Example 16 (a) above butusing3-{6-[4-(1-methyl)ethoxyphenyl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}propionicacid [Example 25(b)] there was prepared3-{6-[4-(1-methyl)ethoxyphenyl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}propanolas a yellow solid (7 mg). MS: 312 (MH⁺). HPLC (Method C): R_(T)=2.9minutes.

EXAMPLE 17

[0621] (a)2-(5-Methoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridine

[0622] A solution of2-(5-methoxy-1-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[1.45 g, Reference Example 13(b)] in methanol (100 mL) was treated withpotassium hydroxide (5N, 15 mL) then heated at reflux for 2 hours. Thereaction mixture was cooled then evaporated. The residue was treatedwith water (150 mL) and the resulting solid was filtered then dried togive the title compound (0.75 g) as a tan solid, m.p. 226-227° C. MS:278 (MH⁺).

[0623] (b) By proceeding in a manner similar to Example 17(a) above butusing3-{1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-propane-1,2-diol[Reference Example 16], there was prepared3-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yloxy]-propane-1,2-diolas a colourless solid, m.p. 202-203° C. MS: 338 (MH⁺).

[0624] (c) By proceeding in a manner similar to Example 17(a) above butusing3-{1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-propan-1-ol[Reference Example 17], there was prepared3-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yloxy]-propan-1-olas a yellow solid, m.p. 192-193° C. MS: 322 (MH⁺).

[0625] (d) By proceeding in a manner similar to Example 17(a) above butusing3-{1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-propan-2-ol[Reference Example 17], there was prepared3-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yloxy]-propan-2-olas a yellow solid, m.p. 201-202° C. MS: 322 (MH⁺).

[0626] (e) By proceeding in a manner similar to Example 17(a) above butusing2-[1-methyl-5-(1-trimethylstannanyl-1H-tetrazol-5-yl)-1H-indol-3-yl]-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[Reference Example 20], there was prepared2-[1-methyl-5-(2H-tetrazol-5-yl)-1H-indol-3-yl]-1H-pyrrolo[2,3-b]pyridineas a yellow solid, m.p. 303° C. MS: 316 (MH⁺).

[0627] (f) By proceeding in a manner similar to Example 17(a) above butusing2-[1-methyl-5-(2-methyl-2H-tetrazol-5-yl)-1H-indol-3-yl]-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[Reference Example 21], there was prepared2-[1-methyl-5-(2-methyl-2H-tetrazol-5-yl)-1H-indol-3-yl]-1H-pyrrolo[2,3-b]pyridineas a beige solid, m.p. 299-300° C. (with decomposition). MS: 330 (MH⁺).

[0628] (g) By proceeding in a manner similar to Example 17(a) above butusing2-[1-methyl-5-(1-methyl-1H-tetrazol-5-yl)-1H-indol-3-yl]-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[Reference Example 21], there was prepared2-[1-methyl-5-(1-methyl-1H-tetrazol-5-yl)-1H-indol-3-yl]-1H-pyrrolo[2,3-b]pyridineas a beige solid, m.p. 286-289° C. (with decomposition). MS: 330 (MH⁺).

[0629] (h) By proceeding in a manner similar to Example 17(a) above butusing1-[1-methyl-3-{(1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl}-1H-indol-5-yl]-ethanone[Reference Example 22], there was prepared1-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yl]-ethanone asa beige solid, m.p. 210° C. (with decomposition). MS: 290 (MH⁺).

[0630] (i) By proceeding in a manner similar to Example 17(a) above butusing2-(5,6-dimethoxy-1-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[Reference Example 13(d)], there was prepared2-(5,6-dimethoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridine as abeige solid, m.p. 283-285° C. (with decomposition). MS: 308 (MH⁺).

[0631] (j) By proceeding in a manner similar to Example 17(a) above butusing(S)-3-{1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-propane-1,2-diol[Reference Example 24(a)], there was prepared(S)-3-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yloxy]-propane-1,2-diolas a colourless solid, m.p. 182-185° C. MS: 338 (MH⁺).

[0632] (k) By proceeding in a manner similar to Example 17(a) above butusing(R)-3-{1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-propane-1,2-diol[Reference Example 24(b)], there was prepared(R)-3-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yloxy]-propane-1,2-diolas a colourless solid, m.p. 153-156° C. MS: 338 (MH⁺).

[0633] (l) By proceeding in a manner similar to Example 17(a) above butusing2-[5-(2-methoxy-1-methyl-ethoxy)-1-methyl-1H-indol-3-yl]-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-bpyridine [Reference Example 25], there was prepared2-[5-(2-methoxy-1-methyl-ethoxy)-1-methyl-1H-indol-3-yl]-1H-pyrrolo[2,3-b]pyridineas a yellow solid, m.p. 150-151° C. MS: 336 (MH⁺).

[0634] (m) By proceeding in a manner similar to Example 17(a) above butusing2-[1-methyl-5-(5-methyl-[1,2,4]oxadiazol-3-yl)-1H-indol-3-yl]-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[Reference example 27], there was prepared2-[1-methyl-5-(5-methyl-[1,2,4]oxadiazol-3-yl)-1H-indol-3-yl]-1H-pyrrolo[2,3-b]pyridineas a cream solid, m.p. 290-294° C. MS: 330 (MH⁺).

[0635] (n) By proceeding in a manner similar to Example 17(a) above butusing(S)-3-{6-methoxy-1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-propane-1,2-diol[Reference Example 24(c)], there was prepared(S)-3-[6-methoxy-1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yloxy]-propane-1,2-diolas a cream solid, MS: 368 (MH⁺). HPLC (METHOD A): R_(T) 5.81 minutes.

[0636] (o) By proceeding in a manner similar to Example 17(a) above butusing2-(5-hydroxy-6-methoxy-1-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[Reference Example 28], there was prepared6-methoxy-1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-ol as abrown solid, MS: 294 (MH⁺). HPLC (METHOD A): R_(T) 6.37 minutes.

[0637] (p) By proceeding in a similar manner to Example 17(a) but using2-(5-methoxy-1-methyl-1H-indol-3-yl)-4-phenyl-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[Reference Example 2(m)] there was prepared2-(5-methoxy-1-methyl-1H-indol-3-yl)-4-phenyl-1H-pyrrolo[2,3-b]pyridineas a yellow solid. ¹H NMR [(CD₃)₂SO]; δ 11.98 (1H, s); 8.21 (1H, d,J=3.5 Hz); 7.94 (1H, s); 7.86 (2H, d, J=8.8 Hz); 7.59 (2H, t, J=8.8 Hz);7.47 (2H, m); 7.39 (1H, d, J=1.9 Hz); 7.17(1H, d, J=3.5 Hz); 6.93 (1H,dd, J=8.8, 1.9 Hz); 6.82 (1H, s); 3.84 (3H, s); 3.82 (3H, s).

[0638] (q) By proceeding in a similar manner to Example 17(a) but using2-[5-(pyridin-4-yl)-1-methyl-1H-indol-3-yl]-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine(Reference Example 60) there was prepared2-[1-methyl-5-(pyridin-4-yl)-1H-indol-3-yl]-4-1H-pyrrolo[2,3-b]pyridineas a yellow solid, m.p. 325-330° C. ¹H NMR [(CD₃)₂SO]; δ 8.65 (2H, d,J=7.2 Hz); 8.20 (1H, s); 8.15 (1H, m); 8.04 (1H, s); 7.88 (3H, m); 7.72(2H, m); 7.03 (1H, t, J=7.2 Hz); 6.96 (1H, s); 3.93 (3H, s).

[0639] (r) By proceeding in a similar manner to Example 17(a) above butusing2-(5-methoxy-1-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile[Reference Example 13(h)] there was prepared2-(5-methoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridine-4-carbonitrileas an orange solid, m.p. 304-305° C. ¹H NMR [(CD₃)₂SO]: δ 12.60 (1H, s);8.24 (1H, s); 8.07 (1H, s); 7.50 (3H, m); 6.96 (1H, d, J=8.6 Hz); 6.88(1H, s); 3.91 (3H, s); 3.86 (3H, s).

[0640] (s) By proceeding in a similar manner to Example 17(a) above butusing4-chloro-2-(5-methoxy-1-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[Reference Example 13(i)] there was prepared4-chloro-2-(5-methoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridineas a tan solid, m.p. 250-252° C. MS: 312 (MH⁺).

EXAMPLE 18

[0641] 1-Methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-ylamine

[0642] A stirred solution of[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yl]-carbamic acidtert-butyl ester [0.2 g, Reference Example 30] in dichloromethane wastreated with trifluoroacetic acid (2 mL). After stirring at ambienttemperature for 16 hours the reaction mixture was evaporated. Theresidue was suspended in saturated sodium bicarbonate solution (10 mL)and the resulting solid was filtered then dried to give the titlecompound as a yellow solid, m.p. 247-248° C. MS: 263 (MH⁺).

EXAMPLE 19

[0643] (a)N-[1-Methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yl]-methanesulfonamide

[0644] A solution of1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-ylamine [52.4 mg,Example 18] in dichloromethane (5 mL) was treated with triethylamine (30μl) followed by methane sulfonyl chloride (17 μl). After stirring atambient temperature for 16 hours the reaction mixture was diluted withdichloromethane (10 mL), then washed with water (10 mL), then washedwith brine (10 mL), then dried over magnesium sulfate and thenevaporated. The residual solid was triturated with diethyl ether to givethe title compound as a yellow solid, m.p. 223-224° C. MS: 341 (MH⁺).

[0645] (b) By proceeding in a manner similar to Example 19(a) above butusing acetyl chloride, there was preparedN-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yl]-acetamideas a yellow solid, m.p. 220-221° C. MS: 305 (MH⁺).

EXAMPLE 20

[0646] (a){1-[5-(1-Hydroxymethyl-cyclobutoxy)-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-indol-1-yl]-cyclobutyl}-methanol

[0647] A stirred solution of 1-{1-(cyclobutanecarboxylic acid ethylester)-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-cyclobutanecarboxylicacid ethyl ester [0.54 g, Reference Example 23(d)] in tetrahydrofuran(50 mL) at 0° C. under nitrogen was treated dropwise with a solution oflithium tetrahydridoaluminate in tetrahydrofuran (4.9 mL, 1.0M). Afterstirring for 2 hours at 0° C. the reaction mixture was stood at ambienttemperature for a further 18 hours then treated dropwise with water (20mL) and then filtered through Hyflo Super Cel®, diatomaceous earth. Thefilter pad was washed with ethyl acetate (20 mL), the two-phase filtratewas separated and the aqueous layer was extracted twice with ethylacetate (25 mL). The combined organic phases were washed with brine (25mL), then dried over magnesium sulfate and then evaporated. The residuewas triturated with diethyl ether and the insoluble material wassubjected to flash column chromatography on silica eluting with amixture of dichloromethane and methanol (19:1, v/v) to give the titlecompound (0.19 g) as a cream solid, m.p. 165-166° C. MS: 418 (MH⁺).

[0648] (b) By proceeding in a similar manner to Example 20(a) above butusing{1-[1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indol-5-yloxy]-cyclobutylcarboxylicacid ethyl ester (Reference Example 15(e) there was prepared{1-[1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indol-5-yloxy]-cyclobutyl}-methanolas a brown solid, m.p. 267-271° C. MS: 349(MH⁺).

EXAMPLE 21

[0649] (a)2-(5-Methoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridinemethanesulfonate

[0650] Methane sulfonic acid (70 μl) was added to a solution of2-(5-methoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridine [300 mg,Example 17(a)] in tetrahydrofuran (20 mL) at ambient temperature. Themixture was stirred for 45 minutes and the resultant precipitateisolated by filtration to give the title compound (390 mg), as a yellowsolid, m.p. 256-257° C. [Elemental analysis: C, 57.60; H, 4.77; N,10.90%. Calculated for C₁₃H₁₁N₃O: C, 57.90; H, 5.13; N, 11.25%].

[0651] (b) By proceeding in a manner similar to Example 21(a) above butusing 6-(5-methoxy-1-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine[Example 1(a)], there was prepared6-(5-methoxy-1-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazinemethanesulfonate as a yellow solid, m.p. 245-250° C. MS: 279(MH⁺).

[0652] (c) By proceeding in a manner similar to Example 21(a) above butusing2-[5-methoxy-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-indol-1-yl]-1-morpholin-4-yl-ethanone[Example 14(a)], there was prepared2-[5-methoxy-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-indol-1-yl]-1-morpholin-4-yl-ethanonemethanesulfonate as a yellow solid, m.p. 214-215° C. MS: 391(MH⁺).

[0653] (d) By proceeding in a manner similar to Example 21(a) above butusing 1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylicacid (2-hydroxy-1,1-dimethyl-ethyl)-amide [Example 14(m)], there wasprepared1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxylic acid(2-hydroxy-1,1-dimethyl-ethyl)-amide methanesulfonate as a yellow solid,m.p. 190-192° C. MS: 363(MH⁺).

[0654] (e) By proceeding in a similar manner to Example 21(a) but using1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylic acid(2-hydroxy-1,1-dimethyl-ethyl)-amide [Example 14(s)] there was prepared2-[5-(2-hydroxy-1,1-dimethylethylcarbamoyl)-1-methyl-1H-indol-3-yl]-1H-pyrrolo[2,3-b]pyrazinemethanesulfonate as a brown solid, m.p. 240° C. (with decomposition). ¹HNMR [(CD₃)₂SO]: δ 8.50 (1H, s); 8.37 (1H, d, J=3.0 Hz); 8.32 (1H, d,J=3.0 Hz); 8.29 (1H, s); 7.82 (1H, d, J=8.2 Hz); 7.77 (1H, s); 7.64 (1H,d, J=8.2 Hz); 7.20 (1H, s); 3.95 (3H, s); 3.59 (2H, s); 2.37 (3H, s);1.38 (6H, s).

[0655] (f) By proceeding in a similar manner to Example 21(a) but using2-[5-methoxy-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-indol-1-yl]-1-morpholin-4-yl-ethanone(Example 12) there was prepared2-[5-methoxy-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-indol-1-yl]-1-morpholin-4-yl-ethanonemethanesulfonate, m/p. 250° C. ¹H NMR [(CD₃)₂SO]: δ 8.32 (1H, s); 8.22(1H, s); 8.11 91H, s); 7.50 (1H, s); 7.44 (1H, d, J=8.8 Hz); 7.04 (1H,s); 6.93 91H, d, J=8.8 Hz); 5.36 (2H, s); 3.90 (3H, s); 3.61 (8H, m);2.31 (3H, s).

EXAMPLE 22

[0656]5-[6-(4-tert-Butylphenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl]ethyl-2H-tetrazole

[0657] To a stirred solution of3-[6-(4-tert-butylphenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propionitrile[0.2 g, Example 23] in toluene (25 mL), at room temperature undernitrogen, was added azidotributyltin (0.61 mL). The reaction mixture washeated at 117° C. After 24 hours, an additional aliquot ofazidotributyltin (0.21 mL) was added and the reaction mixture was heatedfor a further 24 hours. The reaction mixture was quenched with glacialacetic acid (44 mL) and stirred for 15 minutes before partitioningbetween water and ethyl acetate. The two layers were separated and theorganic fraction was washed with water, dried over magnesium sulfate andthen evaporated. The residue was subjected to flash columnchromatography on silica eluting with ethyl acetate to give the titlecompound (0.06 g) as an off-white solid. MS: 348 (MH⁺). HPLC (Method B):R_(T)=1.64 minutes.

EXAMPLE 23

[0658]3-[6-(4-tert-Butylphenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2H-propionitrile

[0659] To a solution of3-[6-(4-tert-butylphenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propionamide[0.1 g, Example 24] in tetrahydrofuran (15 mL) at room temperature wasadded triethylamine (1 mL) and phosphorus oxychloride (1 mL). Thereaction mixture was heated at reflux for 30 minutes then poured into a10% solution of sodium hydrogen carbonate. The mixture was extractedwith ethyl acetate and the combined organic extracts were washed withwater, dried over magnesium sulfate and evaporated. The residue wassubjected to flash column chromatography on silica eluting with first amixture of ethyl acetate and pentane (1:1, v/v) then with ethyl acetateto give the title compound as a white solid. m.p. 215-216° C. MS: 305(MH⁺).

EXAMPLE 24

[0660]3-[6-(4-tert-Butylphenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propionamide

[0661] To a solution of3-[6-(4-tert-butylphenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propionic acid[0.51 g, Example 25(a)] in dimethylformamide (15 mL) at room temperatureunder nitrogen was addedO-benzotriazol-1-yl-N,N,N′,N′,-tetramethyluronium tetrafluoroborate(0.54 g) and triethylamine (0.22 mL). Ammonium gas was bubbled throughthe solution for 5 minutes and the stoppered reaction mixture wasallowed to stand at room temperature overnight. The solution was thenpoured into water and extracted with ethyl acetate. The organic extractswere washed with water and dried over sodium sulfate to afford the titlecompound as a white solid without further purification. MS: 323 (MH⁺).HPLC (Method B): R_(T)=4.49 minutes.

EXAMPLE 25

[0662] (a)3-[6-(4-tert-Butylphenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propionic Acid

[0663] To a solution of dimethyl3-[6-(4-tert-butylphenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propionic-1,1-diacid1,1-dicarboxylate [0.4 g, Reference Example 44(a)] in methanol (20 mL)was added 1N sodium hydroxide solution (4 mL). The reaction mixture washeated at 50° C. for 6 hours then allowed to stand at room temperatureovernight. The solvent was removed by evaporation, 6N sulfuric acidsolution (50 mL) was added and the reaction mixture refluxed for 2hours. After cooling, the solution was basified to pH 4 with 1N sodiumhydroxide solution and the resultant precipitate isolated by filtrationand dried under vacuum to afford the title compound (0.26 g) as anoff-white solid without further purification, m.p. 274-275° C. MS: 324(MH⁺).

[0664] (b) By proceeding in a manner similar to Example 25(a) but usingdimethyl3-[6-(4-(1-methyl)ethoxyphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propionic1,1-diacid 1,1-dicarboxylate [Reference Example 44(b)], there wasprepared3-{6-[4-(1-methyl)ethoxyphenyl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}propionicacid as a yellow solid. MS: 326 (MH⁺). HPLC (Method C): R_(T)=1.56minutes.

[0665] (c) By proceeding in a manner similar to Example 25(a) but usingdimethyl 3-[6-(4-fluorophenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propionic1,1-diacid 1,1-dicarboxylate [Reference Example 44(c)], there wasprepared 3-[6-(4-fluorophenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propionicacid as an off-white solid. ¹H NMR [(CD₃)₂SO]: δ 12.3 (s, 1H) 8.4 (d,1H), 8.2 (d,1H), 7.8 (d, 2H), 7.4 (d, 2H), 3.1 (t, 2H), 2.7 (t, 2H). MS:285 (MH⁺).

[0666] (d) By proceeding in a manner similar to Example 25(a) above butusing dimethyl3-[6-(4-methoxyphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propionic1,1-diacid 1,1-dicarboxylate [Reference Example 44(d)], there wasprepared 3-[6-(4-methoxyphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propionicacid as an off-white solid. ¹H NMR [(CD₃)₂SO]: δ 12.0 (s, 1H) 8.3 (d,1H), 8.2 (d,1H), 7.7 (d, 2H), 7.1 (d, 2H), 3.8(s, 3H), 3.05 (t, 2H), 2.6(t, 2H). MS: 297 (MH⁺).

EXAMPLE 26

[0667]3-[6-(4-tert-Butyl-phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propan-1-ol

[0668] To a mixture of 4N hydrochloric acid in dioxane and methanol (5mL 1:1, v/v) was added3-[6-(4-tert-butylphenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propionic acid[0.02 g, Example 25(a)] and the reaction mixture was allowed to stir atroom temperature overnight. After evaporation, the residue was suspendedbetween sodium hydrogen carbonate solution (10%) and ethyl acetate. Thephases were separated and the organic fraction was washed with water anddried over sodium sulfate. After evaporation, the residue was suspendedin diethyl ether (50 mL). Lithium aluminium hydride (0.12 mL of 1Msolution in diethyl ether) was added and the suspension heated to refluxfor 2 hour. An additional aliquot of lithium aluminium hydride (0.12 mLof 1M solution in diethyl ether) was added and the reaction mixture heatfor a further 1 hour. The reaction was quenched with a cold aqueous(10%) solution of potassium hydrogen sulfate added dropwise untilhydrogen evolution ceased, diluted with water and extracted with ether.The combined organic fractions were washed with water, dried over sodiumsulfate and subjected to flash column chromatography on silica elutingwith ethyl acetate to give the title compound (0.035 g) as an off-whitesolid, m.p. 187-189° C. MS: 310 (MH⁺).

EXAMPLE 27

[0669] [2-Methoxy-5-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-phenoxy]acetic AcidEthyl Ester

[0670] To a solution of2-methoxy-5-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-phenol [0.5 g, Example 28]indimethylformamide (10 mL) and cesium carbonate (0.67 g) was added ethylchloroacetate (0.025 g). The reaction mixture was heated at 50° C.overnight. After cooling, the dimethylformamide was removed in vacuo andthe residue partitioned between ethyl acetate and water. The organicfraction was dried over sodium sulfate, evaporated and subjected toflash column chromatography on silica eluting with 2.5% methanol indichloromethane. This product was further triturated with a mixture ofethyl acetate and pentane to give the title compound as a white solid,m.p. 183-184° C. MS: 328 (MH⁺).

EXAMPLE 28

[0671] 2-Methoxy-5-(5H-pyrrolo[2,3-b]pyrazin-6-yl)phenol

[0672] To a solution of6-(3-tert-butyldimethylsilyloxy-4-methoxy)phenyl-5H-pyrrolo[2,3-b]pyrazine[1.0 g, Reference example 49] in tetrahydrofuran (50 mL) was addedtetrabutylammonium fluoride (5.63 mL of a 1M solution intetrahydrofuran). The reaction mixture was stirred at room temperaturefor 3 hours. The tetrahydrofuran was removed under reduced pressure andthe residue was suspended in water. The resultant solid was collected byfiltration and dried under vacuum to afford the title compound as awhite solid (0.56 g) which was used without further purification. MS:242 (MH⁺). HPLC (Method B): R_(T)=3.02 minutes.

EXAMPLE 29

[0673]3-Fluoro-2-(5-methoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridine

[0674] A solution of2-(5-methoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridine [0.1 g,Example 17(a)] in dry tetrahydrofuran (4 mL), at 0° C., was treated withmethyl magnesium bromide (0.042 mL) and after stirring for a further 20minutes at 0° C. this mixture was treated with1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2,2,2]octanebis(tetrafluoroborate) (0.13 g). The reaction mixture was stirred atroom temperature for 4 hours, then stood at room temperature overnight,then heated at 40° C. for 4 hours, then heated at 80° C. for 2 hours,then cooled to room temperature and then partitioned between ethylacetate and water. The aqueous layer was extracted three times withethyl acetate (25 mL). The combined extracts and ethyl acetate layerfrom the partitioning were washed with brine, then dried over magnesiumsulfate and then evaporated. The residue was triturated with ethylacetate to give the title compound (0.057 g) as a white solid, m.p.248-250° C. ¹H NMR [(CD₃)₂SO]: δ 12.20 (1H, s); 8.24 (1H, m); 7.81 (1H,s); 7.79 (1H, d, J=9.6 Hz); 7.46 (1H, d, J=9.6 Hz); 7.27 (1H, s); 7.18(1H, dd, J=13.1, 6.0 Hz); 6.90 (1H, d, J=9.6 Hz); 3.88 (3H, s); 3.80(3H, s).

EXAMPLE 30

[0675] 3-{6-(4-Hydroxyphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl}propionicAcid

[0676] To a solution of dimethyl3-[6-(4-(1-methyl)ethoxyphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propionic1,1-diacid 1,1-dicarboxylate [0.77 g, Reference Example 44(b)] inmethanol (45 mL) was added 1N sodium hydroxide solution (7.7 mL). Thereaction mixture was heated at 50° C. for 6 hours then allowed to standat room temperature overnight. The solvent was removed by evaporation,6N sulfuric acid solution (20 mL) was added and the reaction mixturerefluxed for 12 hours. After cooling, the solution was basified to pH 4with 4N sodium hydroxide solution and the resultant precipitate filteredand dried under vacuum to afford the title compound (0.42 g) as a yellowsolid which was used without further purification. MS: 284 (MH⁺). HPLC(Method C): R_(T)=2.3 minutes.

EXAMPLE 31

[0677] Ethyl3-{6-(4-hydroxyphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl}propionate

[0678] A solution of3-{6-(4-hydroxyphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl}propionic acid(0.02 g) [Example 30] in ethanol (2 mL) was treated with a catalyticamount of paratoluenesulfonic acid. The mixture was refluxed for 4hours, the solvent removed by evaporation and the precipitate filtered.The solid was then taken in ethyl acetate, the organic layer washed withwater, brine, dried over magnesium sulfate and evaporated to give ayellow solid which was subjected to flash chromatography on silica,eluting with ethyl acetate) to give the title compound. MS: 298(MH⁺).HPLC (Method C): R_(T)=2.58 minutes.

EXAMPLE 32 and REFERENCE EXAMPLE 100

[0679]2-(5-Methoxy-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile

[0680] By proceeding in a similar manner to Reference Example 12(a) butusing2-iodo-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile[Reference Example 62(a)] there was prepared the title compound as ayellow solid, m.p. 303-304° C., TLC R_(F)=0.07 (ethyl acetate/heptane1:1) and2-(5-methoxy-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile[Reference Example 100] as a brown oil. MS: 443 (MH⁺). TLC: R_(F)=0.38(ethyl acetate/heptane 1:1).

EXAMPLE 33

[0681] 6-(4-Methylsulfinylphenyl)-5H-pyrrolo[2,3-b]pyrazine

[0682] A stirred suspension of6-(4-methylthiophenyl)-5H-pyrrolo[2,3-b]pyrazine [0.2362 g, Example1(ah)] in dichloromethane (20 mL) was treated with TBA oxone (2.545 g).After 2 hours the resulting orange solution was evaporated. The residuewas subjected to flash chromatography eluting with a mixture of methanoland dichloromethane (1:1, v/v) to give the title compound as a whitesolid. MS: 258 (MH⁺). ¹H NMR [(CD₃)₂SO]: δ 12.66 (1H, s); 8.41 (1H, s);8.24 (3H, m); 7.82 (2H, d, J=8.7 Hz); 7.33 (1H, s); 2.81 (3H, s).

EXAMPLE 34

[0683] 6-(4-Methylsulfonylphenyl)-5H-pyrrolo[2,3-b]pyrazine

[0684] A stirred suspension of6-(4-methylthiophenyl)-5H-pyrrolo[2,3-b]pyrazine [0.125 g, Example1(ah)] in dichloromethane (15 mL) was treated with TBA oxone (1.35 g).After 4 hours the reaction mixture was evaporated. The residue wassubjected to flash chromatography eluting with a mixture of methanol anddichloromethane (1:1, v/v) to give the title compound as a white solid.MS: 274 (MH⁺). ¹H NMR [(CD₃)₂SO]: δ 12.78 (1H, s); 8.44 (1H, s); 8.28(3H, m); 8.04 (2H, d, J=8.8 Hz); 7.40 (1H, s); 3.27 (3H, s).

EXAMPLE 35

[0685]3-(6-(4-tert-Butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)propylamine

[0686] A solution of the3-[6-(4-tert-butylphenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propionamide[0.2 g, Example 24] in dry tetrahydrofuran (20 mL) was treated with asolution of lithium aluminum hydride in diethyl ether (5 mL, 1M). Thesolution was stirred at room temperature for 24 hours then treated withwater (20 mL). This mixture was filtered through celite and the celitewas washed twice with ethyl acetate (20 mL). The combined filtrate andwashings were washed with water, then with brine, then dried overmagnesium sulfate and then evaporated to give the title compound as ayellow solid (0.12 g). MS: 309 (MH⁺). HPLC (Method C): R_(T)=2.54minutes.

EXAMPLE 36

[0687] (a)N-{3-(6-(4-tert-Butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)propyl}acetamide

[0688] A solution of3-(6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)propylamine(0.0324 mmol) [Example 35] in tetrahydrofuran (1.5 mL) was treated withacetyl chloride (0.0324 mmol) and triethylamine (0.0788 mmol). Thesolution was stirred at room temperature for 12 hours and then treatedwith water and ethyl acetate. The organic phase was dried over magnesiumsulfate and then evaporated. The residue was subjected to columnchromatography on silica eluting with ethyl acetate followed by amixture of ethyl acetate and methanol (9:1, v/v)) to give the titlecompound as a yellow solid. MS: 351 (MH⁺). HPLC (Method C): R_(T)=3.05minutes.

[0689] (b) By proceeding in a manner similar to Example 36(a) above butusing cyclopropylcarbonyl chloride, there was preparedN-{3-(6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)propyl}cyclopropylcarboxylicacid amide as a yellow gummy solid. MS: 377 (MH⁺). HPLC (Method C):R_(T)=3.25 minutes.

[0690] (c) By proceeding in a manner similar to Example 36(a) above butusing n-butyroyl chloride, there was preparedN-{3-(6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)propyl}butyramideas a yellow gummy solid. MS: 379 (MH⁺). HPLC (Method C): R_(T)=3.28minutes.

[0691] (d) By proceeding in a manner similar to Example 36(a) above butusing methoxyacetyl chloride, there was preparedN-{3-(6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)propyl}methoxyacetamideas a white solid. MS: 381 (MH⁺). HPLC (Method C): R_(T)=3.15 minutes.

[0692] (e) By proceeding in a manner similar to Example 36(a) above butusing thien-2-ylcarbonyl chloride, there was preparedN-{3-(6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)propyl}thien-2ylcarboxylicacid amide as a yellow solid. MS: 419 (MH⁺). HPLC (Method C): R_(T)=3.28minutes.

EXAMPLE 37

[0693] (a)N-{3-(6-(4-tert-Butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)propyl}-N′n-propylUrea

[0694] A solution of3-(6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)propylamine(0.0324 mmol) [Example 24] in tetrahydrofuran (2 mL) was treated withn-propyl-isocyanate (0.0324 mmol). The solution was stirred at roomtemperature for 12 hours and then treated with water (3 mL). Theresulting precipitate was filtered, then washed with water and thendried under vacuum at 50° C. to give the title compound as a beigesolid. MS: 394 (MH⁺). HPLC (Method C): R_(T)=3.25 minutes.

[0695] b) By proceeding in a manner similar to Example 37(a) above butusing ethyl-isocyanatoacetate, there was preparedN-{3-(6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)propyl}-N′-carboethoxymethylurea as a yellow solid. MS: 437 (MH⁺). HPLC (Method C): R_(T)=3.18minutes.

EXAMPLE 38

[0696]N-{3-(6-(4-tert-Butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)propyl}-N′,N′-diethylUrea

[0697] A solution of3-(6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)propylamine[0.0324 mmol, Example 24] in tetrahydrofuran (1.5 mL) was treated withdiethylcarbamyl chloride (0.0324 mmol) and triethylamine (0.0788 mmol).The solution was stirred at room temperature for 12 hours and water andethyl acetate were added. The layers were separated and the organicsolution was dried over magnesium sulfate. The drying agent was filteredand the solvent was evaporated. The residue was purified by columnchromatography (silica gel, ethyl acetate followed by 10% methanol inethyl acetate) to give the title compound as a yellow solid. MS: 408(MH⁺). HPLC (Method C): R_(T)=3.43 minutes.

EXAMPLE 39

[0698] (a)N-{3-(6-(4-tert-Butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)propyl}methanesulfonamide

[0699] A solution of3-(6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)propylamine[0.0324 mmol, Example 24] in tetrahydrofuran (1.5 mL) was treated withmethanesulfonyl chloride (0.0324 mmol) and triethylamine (0.0788 mmol).The solution was stirred at room temperature for 12 hours and water andethyl acetate were added. The layers were separated and the organicsolution was dried over magnesium sulfate. The drying agent was filteredand the solvent was evaporated. The residue was purified by columnchromatography (silica gel, ethyl acetate followed by 10% methanol inethyl acetate) to give the title compound as a yellow solid. MS: 387(MH⁺). HPLC (Method C): R_(T)=3.23 minutes.

[0700] (b) By proceeding in a manner similar to Example 39(a) above butusing thien-2-ylsulfonyl chloride, there was preparedN-{3-(6-(4-tert-Butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)propyl}thien-2-ylsulfonamideas a yellow solid. MS: 455 (MH⁺). HPLC (Method C): R_(T)=3.56 minutes.

[0701] (c) By proceeding in a manner similar to Example 39(a) above butusing 3,5-dimethylisoxazol-4-ylsulfonyl chloride, there was preparedN-{3-(6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)propyl}dimethylisoxazol-4-ylsulfonamideas a gummy white solid. MS: 468 (MH⁺). HPLC (Method C): R_(T)=3.55minutes.

[0702] (c) By proceeding in a manner similar to Example 39(a) above butusing 1-methylimidazol-4-ylsulfonyl chloride, there was preparedN-{3-(6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)propyl}1-methylimidazol-4-ylsulfonamideas a gummy white solid. MS: 453 (MH⁺). HPLC (Method C): R_(T)=3.13minutes.

REFERENCE EXAMPLE 1

[0703] (a) 5-Methoxy-1-methyl-1H-indole-3-carbonitrile

[0704] 5-Methoxy-1-methyl-1H-indole-3-carbaldehyde [76 g, ReferenceExample 2(a)] and hydroxylamine hydrochloride (55.9 g) were stirredtogether in dimethylformamide (900 mL) under reflux for 1 hour. Themixture was allowed to cool, then poured into water and then extractedwith ethyl acetate. The combined extracts were washed with water thenevaporated to give the title compound (53 g) as a pale brown solid, m.p.100-104° C. ¹H NMR [(CD₃)₂SO]: δ 8.17 (1H, s); 7.54 (1H, d, J=9.0 Hz);7.09 (1H, d, J=2.4 Hz); 6.97 (1H, dd, J=9.0 and 2.4 Hz); 3.82 and 3.84(6H, s).

[0705] (b) By proceeding in a manner similar to Reference Example 1 (a)above but using 1-methyl-5-phenylpyrazole-3-carbaldehyde [ReferenceExample 53(b)] there was prepared 1-methyl-3-cyano-5-phenylpyrazole.

REFERENCE EXAMPLE 2

[0706] (a) 5-Methoxy-1-methyl-1H-indole-3-carbaldehyde

[0707] A solution of 5-methoxyindole-3-carboxaldehyde (80 g) indimethylformamide (1 L) under nitrogen was treated portion-wise withsodium hydride (20.1 g, 60% dispersion in mineral oil) over 15 minutes.After stirring at ambient temperature for 30 minutes the mixture wastreated dropwise with methyl iodide (31.3 mL) over 10 minutes andstirring was then continued for a further 2 hours. The reaction mixturewas poured cautiously into water then extracted with ethyl acetate. Theorganic phase was washed with water, then dried over sodium sulfate andthen evaporated. The residue was triturated with pentane to give thetitle compound (76 g) as a pale brown solid, m.p. 133-134° C. ¹H NMR[(CD₃)₂SO]: δ 9.86 (1H, s); 8.20 (1H, s); 7.60 (1H, d, J=2.6 Hz); 7.50(1H, d, J=8.9 Hz); 6.96 (1H, dd, J=8.9 and 2.6 Hz); 3.86 and 3.80 (6H,s).

[0708] (b) By proceeding in a manner similar to Reference Example 2(a)above but using indole-3-carbonitrile, there was prepared1-methyl-1H-indole-3-carbonitrile, as a colourless crystalline solid,m.p. 61-63° C.

[0709] (c) By proceeding in a manner similar to Reference Example 2(a)above but using indole-5-carbonitrile, there was prepared1-methyl-1H-indole-5-carbonitrile, as a colourless crystalline solid,m.p. 77-79° C.

[0710] (d) By proceeding in a manner similar to Reference Example 2(a)above but using indole-3-carbonitrile and(3-bromopropoxy)-tert-butyldimethylsilane, there was prepared1-[3-(tert-butyl-dimethyl-silanyloxy)-propyl]-1H-indole-3-carbonitrile,as a clear colourless oil, TLC: R_(F)=0.6 (Dichloromethane). ¹H NMR(CDCl₃): δ 7.70 (1H, d, J=8 Hz); 7.56 (1H, s); 7.39 (1H, d, J=8 Hz);7.27 (1H, t, J=8 Hz); 7.22 (1H, t, J=8 Hz); 4.25 (2H, t, J=6 Hz); 3.49(2H, t, J=6 Hz); 1.95 (2H, quintet, J=6 Hz); 0.87 (9H, s); 0.00 (6H, s).

[0711] (e) By proceeding in a manner similar to Reference Example 2(a)above but using 5-methoxy-1H-indole-3-carbonitrile [Reference Example1(a)] and (3-bromopropoxy)-tert-butyldimethylsilane, there was prepared1-[3-(tert-butyl-dimethyl-silanyloxy)-propyl]-5-methoxy-1H-indole-3-carbonitrile,as a clear colourless oil, ¹H NMR [(CD₃)₂SO]: δ 8.18 (1H, s); 7.55 (1H,d, J=9 Hz); 7.09 (1H, d, J=2 Hz); 6.95 (1H, dd, J=9 and 2 Hz); 4.27 (2H,t, J=6 Hz); 3.82 (3H, s); 3.53 (2H, t, J=6 Hz); 1.95 (2H, quintet, J=6Hz); 0.87 (9H, s); 0.00 (6H, s).

[0712] (f) By proceeding in a manner similar to Reference Example 2(a)above but using indole-3-carbonitrile and(2-bromoethoxy)-tert-butyldimethylsilane, there was prepared1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-indole-3-carbonitrile,as a clear colourless oil. TLC: R_(F)=0.65 (dichloromethane).

[0713] (g) By proceeding in a manner similar to Reference Example 2(a)above but using 5-methoxy-1H-indole-3-carbonitrile [Reference Example1(a)] and benzyl bromide, there was prepared1-benzyl-5-methoxy-1H-indole-3-carbonitrile, as a brown solid, MS:263.22 (MH⁺). TLC: R_(F)=0.8 (dichloromethane/methanol: 19/1).

[0714] (h) By proceeding in a manner similar to Reference Example 2(a)above but using 5-methoxy-1H-indole-3-carbonitrile [Reference Example1(a)] and 2-bromoethoxy-dimethyl-tertiarybutylsilane, there was prepared1-[2-(tertiarybutyl-dimethyl-silanyloxy)-ethyl]-5-methoxy-1H-indole-3-carbonitrile,as a pale yellow solid, MS: 331.23 (MH⁺). TLC: R_(F)=0.6 (pentane/ethylacetate: 8/2).

[0715] (i) By proceeding in a manner similar to Reference Example 2(a)above but using 1H-pyrrole-3-carbonitrile (prepared as described inTetrahedron Letters, 1972, 52, 5337-5340), there was prepared1-methyl-1H-pyrrole-3-carbonitrile, as a brown oil, MS: 107 (MH⁺). ¹HNMR [CDCl₃]: δ 7.09 (1H, m); 6.60 (1H, m); 6.40 (1H, m); 3.68 (3H, s).

[0716] (j) By proceeding in a manner similar to Reference Example 2(a)above but using 1H-pyrrole-2-carbonitrile, there was prepared1-methyl-1H-pyrrole-2-carbonitrile as a colourless liquid. MS: 106(MH⁺). ¹H NMR [CDCl₃]: δ 6.80 (1H, m); 6.67 (1H, m); 6.15 (1H, m); 3.79(3H, s).

[0717] (k) By proceeding in a manner similar to Reference Example 2(a)above but using 2-phenyl-1H-pyrrole-4-carbonitrile (prepared asdescribed in Synthetic Communications, 25, (1995) 6, 795-802), there wasprepared 1-methyl-2-phenyl-1H-pyrrole-4-carbonitrile as a cream solid,m.p. 50-51° C. MS: 183 (MH⁺).

[0718] (l) By proceeding in a similar manner to Reference Example 2(a)but using4-methoxy-2-(5-methoxy-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine(Reference Example 39) there was prepared4-methoxy-2-(5-methoxy-1-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridineas a dark oil, HPLC (METHOD A): R_(T) 9.49 minutes. TLC: RF 0.50(pentane/ethyl acetate: 1/1).

[0719] (m) By proceeding in a similar manner to Reference Example 2(a)but using2-(5-methoxy-1H-indol-3-yl)-4-phenyl-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine(Reference Example 12(g)) there was prepared2-(5-methoxy-1-methyl-1H-indol-3-yl)-4-phenyl-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridineas a tan solid. ¹H NMR [(CD₃)₂SO]; δ 8.39 (1H, d, J=4.4 Hz); 7.71 (2H,d, J=7.2 Hz); 7.63 (3H, m); 7.52 (2H, t, J=8.5 Hz); 7.44 (3H, m); 7.29(2H, d, J=7.2 Hz); 6.94 (1H, s); 6.86 (1H, d, J=8.5 Hz); 6.82 (1H, s);3.86 (3H, s); 3.71 (3H, s); 2.29 (3H, s).

REFERENCE EXAMPLE 3

[0720] (a)6-{1-[3-(tert-Butyl-dimethyl-silanyloxy)-propyl]-1H-indol-3-yl}-5H-pyrrolo[2,3-b]pyrazine

[0721] By proceeding in a manner similar to Example 1(a) herein butusing1-[3-(tert-butyl-dimethyl-silanyloxy)-propyl]-1H-indole-3-carbonitrile[Reference Example 2(d)], there was prepared the title compound as asolid, ¹H NMR [(CD₃)₂SO]: δ 12.1-12.2 (1H, broad s); 8.27 (1H, d, J=2.7Hz); 8.14 (1H, s); 8.10, 7.59 (each 1H, d, J=7.8 Hz); 8.09 (1H, d, J=2.7Hz); 7.29, 7.23 (each 1H, td, J=7.1 and 1.1 Hz); 6.96 (1H, s); 4.33 (2H,t, J=7.1 Hz); 3.62 (2H, t, J=6.0 Hz); 2.03 (2H, quintet, J=6.2 Hz); 0.89(9H, s); 0.00 (6H, s). MS: 407(MH⁺).

[0722] (b) By proceeding in a manner similar to Example 1(a) herein butusing1-[3-(tert-butyl-dimethyl-silanyloxy)-propyl]-5-methoxy-1H-indole-3-carbonitrile[Reference Example 2(e)], there was prepared6-{1-[3-(tert-butyl-dimethyl-silanyloxy)-propyl]-5-methoxy-1H-indol-3-yl}-5H-pyrrolo[2,3-b]pyrazineas a solid, TLC: R_(F)=0.4 (ethyl acetate/pentane: 1/1). δH (d⁶ DMSO)8.27 (1H, d, 4 Hz); 8.08 (2H, m); 7.50 (2H, m); 6.96 (1H, s); 6.91 (1H,dd, 6, 2 Hz); 4.29 (2H, t, 6 Hz); 3.89 (3H, s); 3.61 (2H, t, 6 Hz); 2.00(2H, m); 0.89 (9H, s); 0.03 (6H, s).

[0723] (c) By proceeding in a manner similar to Example 1(a) herein butusing1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-indole-3-carbonitrile[Reference Example 2(f)], there was prepared6-{1-[3-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-indol-3-yl}-5H-pyrrolo[2,3-b]pyrazineas a solid, TLC: R_(F)=0.3 (ethyl acetate/pentane: 1/1). MS: 393 (MH⁺).

[0724] (d) By proceeding in a manner similar to Example 1(a) herein butusing1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-5-methoxy-1H-indole-3-carbonitrile[Reference Example 2(h)], there was prepared6-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-5-methoxy-1H-indol-3-yl}-5H-pyrrolo[2,3-b]pyrazineas a brown solid, TLC: R_(F)=0.4 (dichloromethane/methanol: 19/1). MS:423 (MH⁺).

REFERENCE EXAMPLE 4

[0725] 3-[3-(5H-Pyrrolo[2,3-b]pyrazin-6-yl)-indol-1-yl]-propylbromide

[0726] To a solution of3-[3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-indol-1-yl]-propan-1-ol [1 g,Example 2(a)] and carbon tetrabromide (1.59 g) in dichloromethane (40mL) at ambient temperature was added a solution of triphenylphosphine(1.1 g) in dichloromethane (10 mL) over 2 minutes. The reaction mixturewas stirred at ambient temperature for 3 hour, then stood for 18 hoursand then evaporated to give the title compound which was used withoutfurther purification.

REFERENCE EXAMPLE 5

[0727] Indolizine-1-carbonitrile

[0728] A mixture of 2-pyridylacetontrile (5 g), and chloroacetaldehyde(4.42 g of 50% wt. solution in water) was heated at reflux in1,4-dioxane (25 mL) for 5.5 hours. The reaction mixture was allowed tocool to ambient temperature then evaporated. The residue was partitionedbetween ethyl acetate (100 mL) and hydrochloric acid (100 mL, 1M). Theaqueous layer was extracted twice with ethyl acetate (100 mL). Thecombined organic phases were washed with brine (50 mL), then dried overmagnesium sulfate and then evaporated. The residue was subjected toflash column chromatography on silica eluting with dichloromethane togive the title compound (1.83 g) as a colourless solid, m.p. 53-54° C.MS: 143 (MH⁺).

REFERENCE EXAMPLE 6

[0729] 3-Methyl-indolizine-1-carbonitrile

[0730] A solution of propionaldehyde (36 mL) in diethyl ether (200 mL)and 1,4-dioxane (1.7 mL) at 5° C. under nitrogen was treated dropwisewith bromine (24.7 mL) over 2 hours whilst maintaining the temperatureat 5° C. After the addition was complete, the reaction mixture wasstirred for a further 30 minutes and then washed carefully withsaturated sodium bicarbonate solution (100 mL). The organic phase wasdried over sodium sulfate then concentrated in vacuo at 10° C. and thenadded immediately to a solution of 2-pyridylacetonitrile (8.36 mL) inacetone (50 mL). The resultant mixture was heated at reflux undernitrogen for 6 hours, then allowed to stand at ambient temperatureovernight and then evaporated. The residue was partitioned between ethylacetate (500 mL) and hydrochloric acid (100 mL, 1M). The organic layerwas washed with brine (100 mL) and then evaporated. The residue wassubjected to flash column chromatography on silica eluting with amixture of ethyl acetate and pentane (1:4, v/v) and then triturated withdiethyl ether to give the title compound (4.0 g) as a white solid, m.p.98-100° C. MS: 157(MH⁺).

REFERENCE EXAMPLE 7

[0731] Sodium-1-formyl-piperidine-2-carboxylate

[0732] To a solution of piperidine-2-carboxylic acid (30 g) in formicacid (230 mL) was added acetic anhydride (147 mL) dropwise. Theresultant exotherm was controlled by cooling the reaction mixture in anice/water bath. After stirring at ambient temperature for 24 hours thereaction mixture was diluted with water (20 mL) and then concentrated invacuo. The resultant oil was dissolved in a mixture of methanol (50 mL)and acetonitrile (500 mL). Sodium hydroxide solution (10M, 23 mL) wasadded and the reaction mixture stirred for 8 hours. The resultantprecipitate was filtered, washed with acetonitrile, and ethyl acetateand dried in a vacuum oven to afford the title compound as a white solidwhich was used immediately without further purification.

REFERENCE EXAMPLE 8

[0733] 5,6,7,8-Tetrahydro-indolizine-1-carbonitrile

[0734] To a solution of sodium-1-formyl-piperidine-2-carboxylate (2.0 g)(Reference Example 7) in dichloromethane (50 mL) at ambient temperatureunder nitrogen was added para-toluenesulfonyl chloride (2.31 g). Afterstirring for 10 minutes the mixture was treated dropwise withacrylonitrile (0.88 mL) and triethylamine (1.5 mL) and stirring wascontinued for a further 1 hour when a second portion of triethylamine(1.0 mL) was added. The reaction mixture was stirred for 18 hours andthe dichloromethane removed in vacuo. The residue was taken up in water(50 mL) and extracted with ethyl acetate (200 mL). The combined organicextracts were evaporated in vacuo and the residue was subjected to flashcolumn chromatography on silica eluting with a mixture of ethyl acetateand pentane (1:4, v/v) to give the title compound (1.38 g) as an orangeoil, MS: 147 (MH⁺). ¹H NMR(CDCl₃): δ 6.48 (1H, d, J=3.1 Hz); 6.36 (1H,d, J=3.1 Hz); 3.91 (2H, t, J=6.0 Hz); 2.89 (2H, t, J=6.0 Hz); 1.98 (2H,m); 1.88 (2H, m).

REFERENCE EXAMPLE 9

[0735] (a) 1-(Toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine

[0736] To a solution of 7-azaindole (25 g), para-toluenesulfonylchloride (44.5 g) and a catalytic amount of tetrabutylammoniun sulfatein dry toluene (300 mL) was added sodium hydroxide (160 g in 500 mL ofwater). The biphasic solution was stirred at ambient temperature for 3hours then extracted twice with toluene (100 mL). The combined extractswere dried over magnesium sulfate then concentrated under vacuo. Theresultant solid was triturated with diethyl ether then dried at 60° C.under vacuo to yield the title compound (39.74 g) as a pale yellowsolid, m.p. 136-138° C.

[0737] (b) By proceeding in a similar manner to Reference Example 9(a)but using 4-nitro-1H-pyrrolo[2,3-b]pyridine (prepared according to theprocedure described by A. Ippolito et al., J. Med. Chem. (1982), 25(10),1258-61) there was prepared4-nitro-1-(1-toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine as an orangesolid, m.p. 145-146° C. HPLC (METHOD A):: R_(T)=10.80 minutes.

[0738] (c) By proceeding in a similar manner to Reference Example 9(a)but using 4-chloro-1H-pyrrolo[2,3-b]pyridine(Reference Example 64) therewas prepared 4-chloro-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridineas a white solid. MS: 307 (MH⁺). ¹H NMR (CDCl₃): δ 8.3 (d, 1H), 8.05 (d,2H), 7.8 (d,1H), 7.3 (d, 2H), 7.2 (d, 1H), 6.7 (d, 1H), 2.4 (s, 3H).

[0739] (d) By proceeding in a similar manner to Reference Example 9(a)but using 5-bromo-1H-pyrrolo[2,3-b]pyridine there was prepared5-bromo-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine as a whitesolid, m.p. 138-140° C.

[0740] (e) By proceeding in a similar manner to Reference Example 9(a)but using 4-phenyl-1H-pyrrolo[2,3-b]pyrazine (Reference Example 42)there was prepared4-phenyl-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyrazine as a whitesolid. ¹H NMR [(CD₃)₂SO]: δ 8.44 (1H, d, J=4.5Hz); 8.04 (2H, d,J=8.2Hz); 7.98 (1H, d, J=4.5Hz); 7.69 (2H, d, J=6.8Hz); 7.57 (tt, J=6.2,1.8Hz); 7.51 (1H, tt, J=6.8, 1.8Hz); 7.44 (2H, d, J=8.2Hz); 7.42 (1H, d,J=4.5Hz); 6.92 (1H, d, J=4.5Hz) which was without further purification

REFERENCE EXAMPLE 10

[0741] 2-Iodo-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine

[0742] A solution of 1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine154.4 g, Reference Example 9(a)] in dry tetrahydrofuran (1200 mL) cooledto −78° C., was treated with a solution of butyllithium in hexanes(2.5M, 92 mL) over a 20 minute period. The solution was maintained at−78° C. for 30 minutes, then a solution of iodine (101 g) intetrahydrofuran (600 mL) was added until the iodine colour persisted(ca.300 mL). The mixture was allowed to warm slowly to ambienttemperature and the solvent removed under vacuo. The residue waspartitioned between ethyl acetate (1000 mL) and water (500 mL) and thewater re-extracted with ethyl acetate (2×500 mL). The organic extractswere combined, dried over sodium sulfate and removed under reducedpressure to give a yellow solid which was triturated with diethyl etherto give the title compound (79.6 g) as a pale yellow solid. m.p.105-107° C. MS: 399(MH⁺).

REFERENCE EXAMPLE 11

[0743] (a) 3-Bromo-5-methoxy-indole-1-carboxylic Acid tert-Butyl Ester

[0744] A solution of 5-methoxyindole (10 g) in dry dimethylformamide(150 mL) at ambient temperature was treated with bromine (4 mL) dropwiseensuring the temperature did not rise above 30° C. The mixture wastreated immediately with triethylamine (28 mL) and4-dimethylaminopyridine (0.5 g) followed by a solution ofdi-tert-butyldicarbonate (18 g) in dry dimethylformamide (80 mL) andstirring was continued for a further 4 hours. The reaction mixture wasevaporated and the residue was partitioned between ethyl acetate (250mL) and water (200 mL). The aqueous layer was extracted with ethylacetate (100 mL). The combined organic phases were washed with water(100 mL), then with brine (100 mL), then dried over magnesium sulfateand then evaporated. The residue was subjected to flash columnchromatography on silica eluting with a mixture of pentane and ethylacetate (19/1, v/v) to give the title compound (23.4 g) as a colourlesssolid, m.p. 111-112° C.

[0745] (b) By proceeding in a manner similar to Reference Example 11(a)above but using 5-cyano-indole, there was prepared3-bromo-5-cyano-indole-1-carboxylic acid tert-butyl ester as a greysolid, m.p. 172-174° C. MS: 322(MH⁺).

[0746] (c) By proceeding in a manner similar to Reference Example 11(a)above but using 5,6-dimethoxy-indole, there was prepared3-bromo-5,6-dimethoxy-indole-1-carboxylic acid tert-butyl ester as alilac solid. TLC: R_(F)=0.6 (pentane/ethyl acetate: 19/1).

[0747] (d) By proceeding in a manner similar to Reference Example 11(a)above but using 5-benzyloxy-6-methoxy-indole [prepared according to themethod described by Benigni, J. D. and Minnis, R. L., Heterocycles, 387,2, 1965 ] there was prepared5-benzyloxy-3-bromo-6-methoxy-indole-1-carboxylic acid tert-butyl esteras a colourless solid. MS: 433(MH⁺). HPLC (METHOD A): R_(T)=13.99minutes.

[0748] (e) By proceeding in a manner similar to Reference Example 11(a)above but using 5-amino-indole and an excess of di-tert-butyldicarbonatethere was prepared3-bromo-5-tert-butoxycarbonylamino-indole-1-carboxylic acid tert-butylester as an orange oil. MS: 412(MH⁺). TLC: R_(F)=0.8 (pentane/ethylacetate: 9/1).

[0749] (f) By proceeding in a manner similar to Reference Example 11(a)above but using 1H-indole-6-carboxylic acid methyl ester [ReferenceExample 31] there was prepared 3-bromoindole-1,6-dicarboxylic acid1-tert-butyl ester 6-methyl ester as a pale violet solid, m.p. 117-119°C. MS: 355(MH⁺).

REFERENCE EXAMPLE 12

[0750] (a)2-(5-Methoxy-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine

[0751] A stirred solution of 3-bromo-5-methoxy-indole-1-carboxylic acidtert-butyl ester [50 g, Reference Example 11(a)] in tetrahydrofuran (800mL), under nitrogen, was treated with tributylborate (49.5 mL) thencooled to −100° C. and then treated with a solution of n-butyllithium inhexanes (94 mL, 2.5M) whilst keeping the temperature below −90° C. Oncethe addition was complete the mixture was allowed to warm slowly to roomtemperature over 1 hour and quenched by the addition of ice (10 g). Theorganics were removed under reduced pressure and the residue waspartitioned between ethyl acetate (500 mL) and water (400 mL). Theorganic layer was dried over magnesium sulfate and then evaporated. Theresulting boronic acid, a cream coloured solid (28 g), was dissolved indimethylformamide (600 mL) and the solution was treated with2-iodo-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine [38.3 g,Reference Example 10], then with saturated aqueous sodium bicarbonate(200 mL) and then with tetrakis(triphenylphosphine)palladium[0] (3 g).The mixture was heated at reflux for 4 hours then allowed to cool toambient temperature then concentrated to remove the dimethylformamide.The residue was partitioned between water (400 mL) and ethyl acetate(500 mL) and the aqueous was extracted twice with ethyl acetate (300mL). The combined organics were dried over sodium sulfate thenevaporated. The residual brown gum was triturated with ethyl acetate togive the title compound (27 g) as a pale green solid. MS: 418.43(MH⁺).

[0752] (b) By proceeding in a manner similar to Reference Example 12(a)above but using 3-bromo-5-cyano-indole-1-carboxylic acid tert-butylester [Reference Example 11(b)], there was prepared3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indole-5-carbonitrileas a colourless solid, m.p. 209-214° C. MS: 413 (MH⁺).

[0753] (c) By proceeding in a manner similar to Reference Example 12(a)above but using 3-bromo-5,6-dimethoxy-indole-1-carboxylic acidtert-butyl ester [Reference Example 11(c)], there was prepared2-(5,6-dimethoxy-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridineas a brown solid, MS: 446 (M-H⁺).

[0754] (d) By proceeding in a manner similar to Reference Example 12(a)above but using 5-benzyloxy-3-bromo-6-methoxy-indole-1-carboxylic acidtert-butyl ester [Reference Example 11(d)], there was prepared2-(5-benzyloxy-6-methoxy-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridineas a colourless solid. MS: 524(MH⁺). HPLC (METHOD A)::R_(T)=10.09minutes.

[0755] (e) By proceeding in a manner similar to Reference Example 12(a)above but using 3-bromo-5-tert-butoxycarbonylamino-indole-1-carboxylicacid tert-butyl ester [Reference Example 11(e)], there was prepared{3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yl}-carbamicacid tert-butyl ester as a tan solid. MS: 503(MH⁺). TLC: R_(F)=0.62(pentane/ethyl acetate: 1/1).

[0756] (f) By proceeding in a manner similar to Reference Example 12(a)above but using 3-bromo-indole-1,6-dicarboxylic acid 1-tert-butyl ester6-methyl ester [Reference Example 11(f)], there was prepared3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indole-6-carboxylicacid methyl ester as a pale yellow solid, m.p. 214-216° C. MS: 446(MH⁺).

[0757] (g) By proceeding in a similar manner to Reference Example 12(a)but using2-iodo-4-phenyl-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[Reference Example 62(d)] there was prepared2-(5-methoxy-1H-indol-3-yl)-4-phenyl-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridineas a white solid. HPLC (METHOD A): R_(T)=11.63 minutes. MS: 494(MH⁺).

[0758] (h) By proceeding in a similar manner to Reference Example 12(a)but using4-chloro-2-iodo-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[Reference Example 62(b)] there was prepared4-chloro-2-(5-methoxy-1H-indol-3-yl)-p-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridineas a white solid. MS: 452 (MH⁺). ¹H NMR (CDCl₃): δ 8.4 (d, 1H), 7.6 (d,2H), 7.5 (s, 1H), 7.35 (d, 1H), 7.2 (d, 2H), 6.9 (m, 2H), 6.7 (s, 1H),3.8 (s, 3H), 2.3 (s, 3H).

[0759] (i) By proceeding in a similar manner to Reference Example 12(a)but using2-iodo-5-phenyl-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[Reference Example 62(c)] there was prepared2-(5-methoxy-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-5-phenyl-1H-pyrrolo[2,3-b]pyridine.MS: 494 (MH⁺).

[0760] (j) By proceeding in a similar manner to Reference Example 12(a)but using4-chloro-2-iodo-1-(para-toluenesulfonyl)-1H-pyrrolo[2,3-b]pyridine[Reference Example 62(b)] and 4-tertbutylphenyl bronic acid there wasprepared4-chloro-2-(4-tertiary-butylphenyll)-1-(para-toluenesulfonyl)-1H-pyrrolo[2,3-b]pyridineas a white solid. MS: 439 (MH⁺). TLC R_(F)=0.78 (ethyl acetate/heptane,1:1).

REFERENCE EXAMPLE 13

[0761] (a){5-Methoxy-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-indol-1-yl}-aceticAcid Ethyl Ester

[0762] A solution of2-(5-methoxy-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[6.6 g, Reference Example 12(a)] in dimethylformamide (100 mL), under anitrogen atmosphere, was treated with sodium hydride (700 mg, 60%dispersion in oil). After stirring at ambient temperature for 30 minutesthe mixture was treated dropwise with ethyl chloroacetate (2.0 mL, 23.75mmol) and stirring was continued for an additional 4 hours. The reactionmixture was evaporated and the residue was partitioned between ethylacetate and water. The organic phase was washed with brine, then driedover sodium sulfate and then evaporated to give the title compound (5.77g) as a yellow solid, MS: 504(MH⁺). HPLC (METHOD A):: R_(T)=11.88minutes.

[0763] (b) By proceeding in a manner similar to Reference Example 13(a)above but using methyl iodide, there was prepared2-(5-methoxy-1-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine,as a yellow solid, m.p. 103-105° C. MS: 432(MH⁺).

[0764] (c) By proceeding in a manner similar to Reference Example 13(a)above but using3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indole-5-carbonitrile[Reference Example 12(b)] and methyl iodide, there was prepared1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indole-5-carbonitrile,as a colourless solid, m.p. 189-191° C. MS: 427(MH⁺).

[0765] (d) By proceeding in a manner similar to Reference Example 13(a)above but using2-(5,6-dimethoxy-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[Reference Example 12(c)] and methyl iodide, there was prepared2-(5,6-dimethoxy-1-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine,as a brown solid, MS: 462(MH⁺).

[0766] (e) By proceeding in a manner similar to Reference Example 13(a)above but using2-(5-benzyloxy-6-methoxy-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[Reference Example 12(d)] and methyl iodide, there was prepared2-(5-benzyloxy-6-methoxy-1-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridineas a colourless solid. MS: 538(MH⁺). HPLC (METHOD A):: R_(T)=11.57minutes.

[0767] (f) By proceeding in a manner similar to Reference Example 13(a)above but using{3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yl}-carbamicacid tert-butyl ester [Reference Example 12(e)] and methyl iodide, therewas prepared{1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yl}-carbamicacid tert-butyl ester as a tan solid. MS: 517(MH⁺). TLC: R_(F)=0.7(pentane/ethyl acetate: 1/1).

[0768] (g) By proceeding in a manner similar to Reference Example 13(a)above but using3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indole-6-carboxylicacid methyl ester [Reference Example 12(f)] and methyl iodide, there wasprepared1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indole-6-carboxylicacid methyl ester as a tan solid. MS: 460(MH⁺). TLC: R_(F)=0.6(pentane/ethyl acetate: 1/1).

[0769] (h) By proceeding in a similar manner to Reference Example 13(a)above but using2-(5-methoxy-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile(Reference Example 100) there was prepared2-(5-methoxy-1-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine-4-carbonitrileas a yellow oil. TLC: R_(F)=0.40 (ethyl acetate:heptane 1:1). MS: 457(MH⁺).

[0770] (i) By proceeding in a similar manner to Reference Example 13(a)above but using4-chloro-2-(5-methoxy-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[Reference n Example 12(h)] and methyl iodide, there was prepared4-chloro-2-(5-methoxy-1-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridineas a off-white solid. MS: 466 (MH⁺). ¹H NMR (CDCl₃): δ 8.35 (d,1H); 7.56(d, 2H), 7.39 (s, 1H); 7.16-7.3 (m, 2H), 7.05 (d, 2H), 6.95-7.0 (m, 2H)6.6 (s, 1H) 3.9 (s,3H) 3.8 (s, 3H) 2.3 (s, 3H).

[0771] (j) By proceeding in a similar manner to Reference Example 13(a)above but using2-(5-methoxy-1H-indol-3-yl)-5-phenyl-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[Reference Example 12(i)] and methyl iodide, there was prepared2-(5-methoxy-1-methyl-1H-indol-3-yl)-5-phenyl-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridineas a yellow solid, m.p. 181-183° C. MS: 508 (MH⁺).

REFERENCE EXAMPLE 14

[0772] (a)1-Methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-ol

[0773] To a solution of2-(5-methoxy-1-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[24.5 g, Reference Example 13(b)] in dichloromethane (500 mL), at 0° C.under an atmosphere of nitrogen, was added a solution of borontribromide in dichloromethane (60 mL, 1.0M) and the mixture was stirredat 0° C. for 1 hour. The reaction mixture was allowed to warm slowly toambient temperature and stirring continued for 12 hours. A solution ofsodium carbonate (1M, 250 mL) was added to the mixture and stirring wascontinued vigorously for 3 hours. The precipitated solid was collectedby filtration, washed with dichloromethane (100 mL) and dried to givethe title compound (18.75 g) as a colourless solid, m.p. 256-257° C. MS:418(MH⁺).

[0774] (b) By proceeding in a manner similar to Reference Example 14(a)above but using2-(5-methoxy-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[Reference example 12(a)], there was prepared3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-olas a beige solid, m.p. 188-191° C. MS: 403(MH⁺).

REFERENCE EXAMPLE 15

[0775] (a)2-(5-Allyloxy-1-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine

[0776] A solution of1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-ol[2.1 g, Reference Example 14(a)] in dry dimethylformamide (50 mL) wastreated with potassium tert-butoxide (620 mg) at 0° C. under nitrogen.After stirring for 10 minutes the mixture was treated with allyl bromide(480 μl) and then allowed to warm slowly to ambient temperature.Stirring was continued for a further 6 hours after which time themixture was poured carefully into water and the aqueous phase extractedexhaustively with ethyl acetate. The combined organic extracts werewashed twice with brine (100 mL), then dried over sodium sulfate andthen evaporated. The residue was subjected to flash columnchromatography on silica eluting with a mixture of ethyl acetate andpentane (1:1, v/v) to give the title compound (1.2 g) as a yellow foam,m.p. 257-259° C. MS: 458(MH⁺).

[0777] (b) By proceeding in a manner similar to Reference Example 15(a)above but using ethyl-2-chloroacetate there was prepared{1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-aceticacid ethyl ester as a yellow solid. TLC: R_(F)=0.45 (ethylacetate/pentane: 1/1). MS: 504(MH⁺).

[0778] (c) By proceeding in a manner similar to Reference Example 15(a)above but using ethyl 2-bromoproprionate there was prepared3-{1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-propionicacid ethyl ester as a yellow solid. TLC: R_(F)=0.47 (ethylacetate/pentane: 1/1). MS: 519(MH⁺).

[0779] (d) By proceeding in a manner similar to Reference Example 15(a)above but using ethyl-1-bromocyclobutanecarboxylate there was prepared1-{1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-cyclobutanecarboxylicacid ethyl ester as a colourless solid, m.p. 189-190° C. MS: 544 (MH⁺).

[0780] (e) By proceeding in a similar manner to Reference Example 15(a)above but using 1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indol-5-ol(Example 7) and ethyl 1-bromocyclobutane carboxylate there was prepared{1-[1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indol-5-yloxy]-cyclobutylcarboxylicacid ethyl ester as a tan solid. TLC: R_(F)=0.23(dichloromethane/methanol, 19:1). HPLC (METHOD A): R_(T)=7.71 minutes.

REFERENCE EXAMPLE 16

[0781]3-{1-Methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-propane-1,2-diol

[0782] A solution of2-(5-allyloxy-1-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[45.7 mg, Reference Example 15 (a)] in acetone (10 mL) was treated witha solution of 4-methylmorpholine-N-oxide (6 mg) in water (1 mL). Thismixture was then treated with osmium tetroxide (2.5%/wt in tert-butanol,6 drops) and the mixture stirred at room temperature for 12 hours. Thereaction mixture was diluted with water (75 mL), and extractedexhaustively with ethyl acetate. The combined organics were washed twicewith brine (75 mL), then dried over magnesium sulfate and thenevaporated. The residue was subjected to flash column chromatography onsilica eluting with ethyl acetate to give the title compound (33 mg) asa colourless solid. TLC: R_(F)=0.25 (ethyl acetate). MS: 492(MH⁺).

REFERENCE EXAMPLE 17

[0783]3-{1-Methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-propan-1-oland3-{1-Methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-propan-2-ol

[0784] A solution of2-(5-allyloxy-1-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[91 mg, Reference Example 15(a)] in dry tetrahydrofuran (5 mL) wastreated with a solution of borane-tetrahydrofuran complex intetrahydrofuran(1200 μl, 1.0M). After stirring at ambient temperaturefor 7 hours the reaction mixture was treated with ethanol (9 drops), 5Npotassium hydroxide (4 drops) and hydrogen peroxide (6 drops) andstirring was continued for 12 hours during which time a white solid wasprecipitated. The reaction mixture was diluted with water (50 mL) andthe pH of this mixture was adjusted to 10 by addition of potassiumhydroxide solution (1M) before exhaustively extracting with ethylacetate. The combined organic extracts were dried over sodium sulfatethen evaporated. The residue was subjected to flash columnchromatography on silica eluting with a mixture of ethyl acetate andpentane (2:1, v/v) to give3-{1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-propan-1-ol(50 mg) as a colourless solid [TLC: R_(F)=0.15 (ethyl acetate). MS:476(MH⁺)] and3-[1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-propan-2-ol(8 mg) as a colourless solid. [TLC: R_(F)=0.3 (ethyl acetate); MS:476(MH⁺)].

REFERENCE EXAMPLE 18

[0785] (a) Trifluoro-methanesulfonic Acid1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-ylEster

[0786] A suspension of1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-ol[398 mg, Reference Example 14(a)] in dichloromethane (10 mL), cooled to−78° C. under a nitrogen atmosphere, was treated with triethylamine(0.15 mL) followed by N-phenylyltrifluormethanesulfonimide (1.7 g). Theresultant mixture was allowed to warm slowly to ambient temperature,stirring was continued for a further 12 hours then saturated sodiumbicarbonate (20 mL) was added. The organic phase was separated and theaqueous phase was extracted twice with dichloromethane (20 mL). Thecombined organics were dried over sodium sulfate then evaporated. Theresidue was subjected to flash column chromatography on silica elutingwith a mixture of ethyl acetate and pentane (2:3, v/v) to give the titlecompound (380 mg) as a colourless solid. MS: 492(MH⁺). HPLC (METHOD A):R_(T)=2.02 minutes.

[0787] (b) By proceeding in a similar manner to Reference Example 18(a)but using 1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indol-5-ol(Example 7) there was prepared2-(1-methyl-5-trifluoromethylsulfonyloxyindol-3-yl)-1H-pyrrolo[2,3-b]pyrazineas a purple solid. HPLC (METHOD A):: R_(T)=8.12 minutes. ¹H NMR[(CD₃)₂SO]: δ 12.30 (1H, s); 8.32 (1H, s); 8.27 (1H, d, J=3.5 Hz); 8.23(1H, s); 7.97 (1H, s); 7.76 (1H, d, J=8.6 Hz); 7.08 (1H, s); 3.96 (3H,s).

REFERENCE EXAMPLE 19

[0788] (a)1-Methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indole-5-carboxylicAcid Methyl Ester

[0789] A solution of trifluoro-methanesulfonic acid1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-ylester [300 mg, Reference Example 18(a)] in a mixture of drydimethylformamide (10 mL), methanol (6 mL) and triethylamine (2 mL) wastreated with palladium acetate (24 mg) and 1,3bis(diphenylphosphino)propane and the mixture stirred at ambienttemperature for 30 minutes. Carbon monoxide was introduced via a septumto the reaction vessel at a steady rate and the mixture heated at 90° C.until no starting material was present as indicated by TLC (ethylacetate/pentane: 2/3). The mixture was then concentrated in vacuo andthe residue partitioned between dichloromethane and water. The organicphase was washed with a saturated solution of lithium chloride, thendried over sodium sulfate and then evaporated. The residue was subjectedto flash column chromatography on silica eluting with a mixture of ethylacetate and pentane (2:3, v/v) to give the title compound (200 mg) as acolourless solid. MS: 460(MH⁺). HPLC (METHOD A):: R_(T)=10.23 minutes.

[0790] (b) By proceeding in a similar manner to Reference Example 19(a)but using2-(1-methyl-5-trifluoromethylsulfonyloxyindol-3-yl)-1H-pyrrolo[2,3-b]pyrazine(Reference Example 18(b)) there was prepared methyl1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indole-5-carboxylate as abrown solid. MS 307 (MH⁺). HPLC (METHOD A): R_(T)=6.64 minutes.

REFERENCE EXAMPLE 20

[0791]2-[1-Methyl-5-(1-trimethylstannanyl-1H-tetrazol-5-yl)-1H-indol-3-yl]-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine

[0792] A solution of1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indole-5-carbonitrile[100 mg, Reference Example 13(c)] in toluene (10 mL) was treated withtrimethyltin azide (56 mg, 0.28 mmol) then heated under reflux for 14hours. The white precipitate was collected by filtration washed withtoluene (10 mL) and then dried to give the title compound (125 mg) as acolourless solid, m.p. 240-243° C. (with decomposition). MS: 633(MH⁺).

REFERENCE EXAMPLE 21

[0793]2-[1-Methyl-5-(1-methyl-1H-tetrazol-5-yl)-1H-indol-3-yl]-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridineand2-[1-Methyl-5-(2-methyl-2H-tetrazol-5-yl)-1H-indol-3-yl]-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine

[0794] Methyl iodide (2.5 mL) was added to a solution of2-[1-methyl-5-(1-trimethylstannanyl-1H-tetrazol-5-yl)-1H-indol-3-yl]-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[620 mg, Reference Example 20] at ambient temperature. The mixture wasthen allowed to stir at ambient temperature for 4 hours then was pouredinto water and then extracted with ethyl acetate. The combined extractwas washed with brine, then dried over magnesium sulfate and thenevaporated. The residue was subjected to flash chromatography on silicaeluting with a mixture of ethyl acetate and petroleum ether (1:1, v/v)to give2-[1-methyl-5-(1-methyl-1H-tetrazol-5-yl)-1H-indol-3-yl]-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine(191 mg) as a colourless solid, [MS: 506(MNa⁺). ¹H NMR [(CD₃)₂SO]: δ8.39 (dd, 1H, J=4.8 and 1.6 Hz); 7.97 (m, 1H); 7.96 (d, 1H, J=4.0 Hz);7.90 (s, 1H); 7.80 (dd, 1H, J=8.7 and 0.6 Hz); 7.70 (dd, 1H, J=8.7 and1.8 Hz); 7.56 (m, 2H); 7.30 (dd, 1H, J=7.7 and 4.8 Hz); 7.22 (m, 2H);6.82 (s, 1H); 4.19 (s, 3H); 4.0 (s, 3H); 2.23 (s, 3H)] and2-[1-Methyl-5-(2-methyl-2H-tetrazol-5-yl)-1H-indol-3-yl]-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine(77 mg) as a colourless solid, m.p. 215-218° C. [MS: 506 (MNa⁺)].

REFERENCE EXAMPLE 22

[0795]1-{1-Methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yl}-ethanone

[0796] To dry, degassed dimethylformamide (110 mL) under nitrogen atambient temperature, was added trifluoro-methanesulfonic acid1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-ylester 12.2 g, Reference Example 18], triethylamine (1.15 mL),n-butylvinylether (2.87 mL), 1,3-bis(diphenylphosphinopropane) (413 mg)and palladium acetate (232 mg) sequentially. The mixture was heated atreflux for 2 hours then cooled to ambient temperature and then added tohydrochloric acid (90 mL, 1M). This mixture was extracted withdichloromethane (200 mL). The organic extract was washed with saturatedaqueous sodium bicarbonate, then with brine, then dried over magnesiumsulfate and then evaporated. The residue was subjected to flashchromatography on silica eluting with a mixture of ethyl acetate andpentane (2:3, v/v) to give the title compound (1.1 g) as a yellow solid,m.p. 177-178° C. MS: 444(MH⁺).

REFERENCE EXAMPLE 23

[0797] (a)2-[5-({S}-(+)-2,2-Dimethyl-[1,3]dioxolan-4-ylmethoxy)-1-methyl-1H-indol-3-yl]-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine

[0798] A solution of1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-ol[1.17 g, Reference Example 14(a)] in dry dimethylformamide (50 mL) wastreated with caesium carbonate (1.1 g) and tetrabutylammonium hydrogensulfate (40 mg). After stirring at ambient temperature for 30 minutesthe mixture was treated with(R)-(+)-2,2-dimethyl-1,3-dioxolane-4-ylmethyl-paratoluenesulfonate (0.96g) then heated at 120° C. overnight. The reaction mixture wasconcentrated in vacuo and the residue partitioned twice betweendichloromethane (100 mL) and water (50 mL) and the aqueous layers wereextracted with dichloromethane (100 mL). The combined organic phaseswere washed twice with brine (150 mL), then dried over magnesium sulfateand then evaporated. The residue was subjected to flash chromatographyon silica eluting with a mixture of dichloromethane and methanol (199:1,v/v) to give the title compound (1.04 g) as a yellow oil, MS: 532(MH⁺).¹H NMR [(CD₃)₂SO]: δ 1.30 (3H, s); 1.37 (3H, s); 2.29 (3H, s); 3.76 (1H,dd, J=8.3 and 6.5 Hz); 3.90 (3H, s); 3.94-3.98 (2H, m); 4.10 (1H, dd,J=8.20 and 6.5 Hz); 4.41 (1H, m); 6.74 (1H, s); 6.91 (1H, dd, J=8.8 and2.3 Hz); 6.98 (1H, d, J=2.4 Hz); 7.25 (2H, d, J=7.9 Hz); 7.29 (1H, dd,J=7.8 and 4.9 Hz); 7.44 (1H, d, J=8.8 Hz); 7.56 (1H, d, J=8.3 Hz); 7.63(1H, s); 7.81 (2H, d, J=8.0 Hz); 7.92 (1H, dd, J=7.7 and 1.6 Hz); 8.33.(1H, dd, J=4.9 and 1.7 Hz).

[0799] (b) By proceeding in a manner similar to Example 23(a) above butusing (S)-(−)-2,2-dimethyl-1,3-dioxolane-4-ylmethyl-paratoluenesulfonatethere was prepared2-[5-({R}-(−)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-1-methyl-1H-indol-3-yl1-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridineas a yellow oil, MS: 532 (MH⁺). ¹H NMR [(CD₃)₂SO]: δ 1.33 (3H, s); 1.37(3H, s); 2.29 (3H, s); 3.77 (1H, dd, J=8.3 and 6.5 Hz); 3.88 (3H, s);3.97-3.99 (2H, m); 4.11 (1H, dd, 1J=8.3 and 6.6 Hz); 4.41 (1H, m); 6.74(1H, s); 6.94 (1H, dd, J=8.8 and 2.3 Hz); 6.97 (1H, d, J=2.3 Hz); 7.25(2H, d, J=8.1 Hz); 7.29 (1H, dd, J=7.8 and 4.9 Hz); 7.44 (1H. d. J=8.8Hz); 7.57 (2H, d, J=8.4 Hz); 7.63 (1H, s); 7.95 (1H, dd, J=7.81 and 1.7Hz); 8.33 (1H, dd, J=4.88 and 1.7 Hz).

[0800] (c) By proceeding in a manner similar to Example 23(a) above butusing2-(5-hydroxy-6-methoxy-1-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[Reference Example 28(a)], there was prepared2-[5-({S}-(+)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-6-methoxy-1-methyl-1H-indol-3-yl]-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridineas a cream solid. MS: 548(MH⁺). HPLC (METHOD A):: R_(T)=11.60 minutes.

[0801] (d) By proceeding in a manner similar to Example 23(a) above butusing3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-ol[Reference Example 14(b)] and ethyl 1-bromocyclobutane carboxylate,there was prepared 1-{1-(cyclobutanecarboxylic acid ethylester)-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-cyclobutanecarboxylicacid ethyl ester as a cream solid. MS: 657(MH⁺). ¹H NMR [(CD₃)₂SO]: δ8.35 (1H, dd, J=4.8 and 1.6 Hz); 7.9 (2H, m); 7.48 (3H, m); 7.28 (1H,dd, J=7.7 and 4.8 Hz); 7.24 (2H, d, J=8.4 Hz); 6.71 (1H, dd, J=8.9 and2.4 Hz); 6.68 (1H, s); 6.64 (1H, d, J=2.4 Hz); 5.12 (1H, dd, J=8.8 and8.8 Hz); 4.13-4.03 (4H, m); 3.66 (1H, dd, J=9.4 and 9.4 Hz); 2.64-1.82(13H, m); 1.15 (3H, t, J=7.1 Hz); 0.94 (3H, t, J=7.1 Hz).

REFERENCE EXAMPLE 24

[0802] (a)(S)-3-{1-Methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-propane-1,2-diol

[0803] A solution of2-[5-({R}-(−)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-1-methyl-1H-indol-3-yl]-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[1.04 g, Reference Example 23(b)] in methanol (20 mL) was treated withhydrochloric acid (20 mL, 1M) then heated under reflux for 3 hours. Thereaction mixture was concentrated in vacuo and the residue subjected toflash chromatography on silica eluting with a mixture of ethyl acetateand pentane (2:1, v/v) to give the title compound (380 mg) as a clearoil. TLC: R_(F)=0.2 (pentane/ethyl acetate: 1/2). MS: 492(MH⁺).

[0804] (b) By proceeding in a manner similar to Example 24(a) but using2-[5-({S}-(+)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-1-methyl-1H-indol-3-yl]-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[Reference Example 23(a)] there was prepared(R)-3-{1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-propane-1,2-diolas a clear oil. MS: 492(MH⁺). ¹H NMR [(CD₃)₂SO]: δ 8.33 (1H, dd, 4.9,J=1.7 Hz); 7.92 (1H, dd, J=7.8 and 1.7 Hz); 7.62 (1H, s); 7.56 (2H, d,J=8.8 Hz); 7.45 (1H, d, J=8.8 Hz); 7.29 (1H, dd, J=7.8 and 4.8 Hz); 7.25(2H, d, J=8.1 Hz); 6.96 (1H, d, J=2.3 Hz); 6.92 (1H, dd, J=8.8 and 2.3Hz); 6.75 (1H, s); 4.93 (1H, s); 4.66 (1H, s); 5.13 (1H, d, J=5.13 Hz);3.88 (3H, s); 3.80 (2H, d, J=5.9 Hz); 3.46 (2H, s); 2.23 (3H, s).

[0805] (c) By proceeding in a manner similar to Example 24(a) above butusing2-[5-({S}-(+)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-6-methoxy-1-methyl-1H-indol-3-yl]-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[Reference Example 23(c)] there was prepared(R)-3-{6-methoxy-1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-propane-1,2-diolas a cream solid. MS: 522(MH⁺). HPLC (METHOD A): R_(T)=8.15 minutes.

REFERENCE EXAMPLE 25

[0806]2-[5-(2-Methoxy-1-methyl-ethoxy)-1-methyl-1H-indol-3-yl]-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine

[0807] A solution of triphenylphosphine (470 mg) anddiisopropyldiazodicarboxylate (350 μl) in dry toluene (15 mL) wastreated with1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-ol[150 mg, Reference Example 14(a)] followed by 1-methoxy-2-propanol (150μl). The resulting mixture was heated under reflux for 5 hours thencooled and then evaporated. The residue was subjected to flashchromatography on silica eluting with a mixture of ethyl acetate andpentane (1:1, v/v) to give the title compound (50 mg) as a clear oil.TLC: R_(F)=0.65 (pentane/ethyl acetate: 1/1). MS: 480(MH⁺).

REFERENCE EXAMPLE 26

[0808]N-Hydroxy-1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indole-5-carboxamidine

[0809] A solution of1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indole-5-carbonitrile[2.11 g, Reference Example 13(c)] in ethanol (150 mL) at ambienttemperature was treated with hydroxylamine hydrochloride (1.72 g) andpotassium carbonate (3.43 g). The reaction mixture was heated at refluxunder nitrogen for 15 hours then filtered. The filtrate was evaporatedto give the title compound (2.8 g) as a dark green solid. MS: 460(MH⁺).HPLC (METHOD A): R_(T)=6.19 minutes.

REFERENCE EXAMPLE 27

[0810]2-[1-Methyl-5-(5-methyl-[1,2,4]oxadiazol-3-yl)-1H-indol-3-yl]-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine

[0811] To a suspension ofN-hydroxy-1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indole-5-carboxamidine[0.7 g, Reference Example 26] in toluene (30 mL) at ambient temperatureunder nitrogen was added acetic anhydride (0.467 g). The reactionmixture was heated at reflux for 4.5 hours then filtered. The filtratewas evaporated to give the title compound (0.32 g) as a dark red oilwhich was used immediately without further purification.

REFERENCE EXAMPLE 28

[0812]2-(5-Hydroxy-6-methoxy-[-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-3H-pyrrolo[2,3-b]pyridine

[0813] A solution of2-(5-benzyloxy-6-methoxy-1-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[6.26 g, Reference Example 13(e)] in acetonitrile (500 mL) was treatedwith sodium iodide (4.38 g) followed by trimethylsilyl chloride (3.17mL). The mixture stirred at 40° C. for 3 hours then treated with furtherportions of sodium iodide (4.38 g) and trimethylsilyl chloride (3.17mL). After stirring at 40° C. for a further 12 hours the reactionmixture was evaporated. The residue was treated with water (200 mL) andthe mixture was extracted three times with ethyl acetate (200 mL). Thecombined extracts were dried over magnesium sulfate then evaporated. Theresidual brown foam was triturated with ethyl acetate and diisopropylether to give the title compound (3.04 g) as a light brown solid, m.p.211-214° C. HPLC (METHOD A): R_(T)=9.30 minutes.

REFERENCE EXAMPLE 29

[0814]1-{6-Methoxy-1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-cyclobutanecarboxylicAcid Ethyl Ester

[0815] Sodium hydride (43 mg, 60% dispersion in mineral oil) was addedto a stirred solution of2-(5-hydroxy-6-methoxy-[-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[400 mg, Reference Example 28(a)] in dry dimethylformamide (20 mL) undera nitrogen atmosphere at ambient temperature. The mixture was allowed tostir for 1 hour then treated with ethyl-1-bromocyclobutanecarboxylate(216 μl) and stirring was continued overnight. Additional portions ofsodium hydride (43 mg, 60% dispersion in mineral oil) and ethyl1-bromocyclobutanecarboxylate (216 μl) were then added, then the mixturewas heated at 50° C. for 5 hours. The cooled reaction mixture wasevaporated and the residue was partitioned between ethyl acetate andwater. The organic phase was washed with water, then with brine, thendried over magnesium sulfate and then evaporated. The yellow residue wassubjected to flash chromatography on silica eluting with a mixture ofethyl acetate and pentane (2:3, v/v) to give the title compound (266 mg)as a yellow oil. MS: 576(MH⁺). HPLC (METHOD A):: R_(T)=11.07 minutes.

REFERENCE EXAMPLE 30

[0816][1-Methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yl]-carbamic Acidtert-Butyl Ester

[0817] A solution of{1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yl}-carbamicacid tert-butyl ester [0.3 g, Reference Example 13(f)] in methanol (15mL) was treated with potassium hydroxide solution (5N, 2 mL) then heatedat reflux for 4 hours. The reaction mixture was evaporated and theresidue triturated with water to give the title compound (0.2 g) as atan solid. MS: 263(MH⁺). TLC: R_(F)=0.3 (ethyl acetate).

REFERENCE EXAMPLE 31

[0818] 1H-Indole-6-carboxylic Acid Methyl Ester

[0819] A solution of 1H-indole-6-carboxylic acid (10 g) in methanol (300mL) was treated with concentrated sulfuric acid (0.5 mL) then heated ona steam bath for 10 hours. The solvent was removed under reducedpressure and the residue partitioned between saturated sodiumbicarbonate solution (150 mL) and dichloromethane (150 mL). The aqueouslayer was further extracted twice with dichloromethane (150 mL). Thecombined organics were dried over sodium sulfate then evaporated. Theresidue was subjected to flash chromatography on silica eluting with amixture of ethyl acetate and pentane (7:3, v/v) to give the titlecompound (7.4 g) as a white solid, m.p. 79-81° C. MS: 176(MH⁺).

REFERENCE EXAMPLE 32

[0820] Dimethyl-(6-phenyl-5H-pyrrolo[2,3-b]pyrazin-7-ylmethyl)-amine

[0821] A solution of dimethylamine in tetrahydrofuran (0.5 mL, 2.0M) at0° C. was treated with glacial acetic acid (15 μl) then withformaldehyde (75 μl, 40% solution). After stirring at 0° C. for 10minutes this mixture was treated with 6-phenyl-5H-pyrrolo[2,3-b]pyrazine[0.195 g, Example 2(c)] and then with tetrahydrofuran (3 mL) to ensurecomplete dissolution. The reaction mixture was allowed to warm toambient temperature, then stirred overnight, then diluted with ethylacetate (5 mL) and then extracted three times with hydrochloric acid (5mL, 1N). The combined acid extracts were adjusted to pH 6-7 by additionof potassium hydroxide solution (5N). The resulting pale yellow solidwas filtered, then washed with water and then dried to give the titlecompound (0.16 g) as a pale yellow solid, m.p. 191-192° C.

REFERENCE EXAMPLE 33

[0822] Trimethyl-(6-phenyl-5H-pyrrolo[2,3-b]pyrazin-7-ylmethyl)-ammoniumIodide

[0823] A solution ofdimethyl-(6-phenyl-5H-pyrrolo[2,3-b]pyrazin-7-ylmethyl)-amine [5.1 g,Reference Example 32] in ethyl acetate (100 mL) at 0° C. was treatedwith a solution of iodomethane (40 mL) in ethanol (150 mL). Theresulting mixture was stirred at 0° C. for 2 hours. The precipitatedsolid was filtered then washed with ethyl acetate (10 mL) and then withdiethyl ether (20 mL) to give the title compound as a yellow solid (4.5g), m.p. 224-225° C.

REFERENCE EXAMPLE 34

[0824] (6-Phenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl)-acetonitrile

[0825] A solution of potassium cyanide (0.84 g) in water (20 mL) wasadded rapidly to a stirred solution oftrimethyl-(6-phenyl-5H-pyrrolo[2,3-b]pyrazin-7-ylmethyl)-ammonium iodide[1.1 g, Reference Example 33] in dimethylformamide (20 mL) and themixture heated at 75° C. for 6 hours. The cooled solution was dilutedwith water (100 mL) and the precipitated solid filtered to give thetitle compound as a yellow solid, m.p. 247-248° C.

REFERENCE EXAMPLE 35

[0826] (6-Phenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl)-acetic Acid

[0827] A solution of(6-phenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl)-acetonitrile [70 mg, ReferenceExample 34] in potassium hydroxide (10M, 5 mL) was heated at 100° C. for1.5 hours. The reaction mixture was allowed to cooled, then diluted withwater (25 mL) and then acidified to pH 1 by addition of concentratedhydrochloric acid. The resulting pale yellow solid was filtered, thenwashed with water and then dried to give the title compound (40 mg) as ayellow solid, m.p. 276-277° C.

REFERENCE EXAMPLE 36

[0828]1-Methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indole-5-carbaldehyde

[0829] To a solution of1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indole-5-carbonitrile[500 mg, Reference Example 13(c)] in tetrahydrofuran (20 mL) at 0° C.was added diisobutylaluminium hydride (12 mL, 1M in tetrahydrofuran)under an atmosphere of nitrogen. The resultant solution was then allowedto warm to ambient temperature and stirred at this temperature for 2hours. The reaction mixture was then poured into a solution of cold 1Naqueous hydrochloric acid (20 mL). After 1 hour, the mixture was madealkaline with saturated aqueous sodium hydroxide and extracted withethyl acetate (40 mL). The organic layer was separated and the aqueousfurther extracted with ethyl acetate (2×20 mL). The organic extractswere combined, dried over magnesium sulfate and concentrated in vacuo togive the title compound (221 mg) as a white solid, m.p. 188-189° C. MS:430 (MH⁺).

REFERENCE EXAMPLE 37

[0830]3-{1-Methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yl}-acrylicAcid Ethyl Ester

[0831] Triethylphosphonoacetate (60 mL) was added at 0° C. to asuspension of sodium hydride (22.4 mg, 60% dispersion in mineral oil) indimethoxyethane (3 mL). The resultant suspension was stirred at ambienttemperature for 1 hour.1-Methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indole-5-carbaldehyde[120 mg, Reference Example 36] in dimethoxyethane (2 mL) was added andstirring was continued for 3 hours. The reaction mixture was then pouredinto water and extracted with ethyl acetate (2×30 mL). The combinedorganics were then washed with brine before drying over magnesiumsulfate and then concentrated in vacuo to give the title compound (126mg) as a yellow solid, m.p. 159-162° C. MS: 500 (MH⁺).

REFERENCE EXAMPLE 38

[0832] (a)3-{1-Methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yl}-propionicAcid Ethyl Ester

[0833] Palladium (15.7 mg, 10% on activated carbon) was added to asuspension of3-{1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yl}-acrylicacid ethyl ester [100 mg, Reference Example 37] in industrial methylatedspirit (25 mL). The resultant suspension was then stirred under anatmosphere of hydrogen for 16 hours. The reaction mixture was thenfiltered through a pad of celite and the filtrate evaporated in vacuo.The resultant solid was triturated with water, filtered and dried togive the title compound (92 mg) as a white solid, m.p. 280-282° C. MS:502 (MH⁺).

[0834] (b) By proceeding in a manner similar to Example 38 (a) above butusing ethyl3-[2-dimethylamino-5-(5H-pyrrolo[2,3-b]pyrazin-6-yl)phenyl]prop-2-enonate(Reference Example 47), there was prepared ethyl3-[2-dimethylamino-5-(5H-pyrrolo[2,3-b]pyrazin-6-yl)phenyl]propionate asan orange gum which was used directly in the next reaction. ¹H NMR[(CD₃)₂SO]; δ 8.33 (1H, s); 8.17 (1H, s); 7.94 (1H, s); 7.82 (1H, d,J=8.4 Hz); 7.20 (1H, d, J=8.4 Hz); 7.03 (1H, s); 4.07 (2H, q, J=7.6 Hz);3.38 (2H, t, J=7.1 Hz); 3.00 (2H, t, J=7.1 Hz); 2.70 (6H, s); 1.19 (3H,t, J=7.1 Hz).

REFERENCE EXAMPLE 39

[0835]4-Methoxy-2-(5-methoxy-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine

[0836] By proceeding in a similar manner to Example 18 but using2-(1-N-tertbutyloxycarbonyl-5-methoxy-1H-indol-3-yl)-4-methoxy-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine(Reference Example 40) there was prepared the title compound as a tansolid. HPLC (METHOD A):: R_(T)=8.49 minutes. MS: 448 (MH⁺).

REFERENCE EXAMPLE 40

[0837]2-(1-tert-Butyloxycarbonyl-5-methoxy-1H-indol-3-yl)-4-methoxy-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine

[0838] A stirred solution of diisopropylamine (0.21 mL) intetrahydrofuran (5 mL), at −70° C. and under nitrogen, was treated witha solution of n-butyllithium in hexanes (0.6 mL, 2.5M) over 5 minutes,whilst maintaining the temperature below −65° C. After stirring for 1hour the mixture was added, at −30° C., to a solution of4-methoxy-1-(1-toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine (ReferenceExample 41, 280 mg) in tetrahydrofuran (10 mL), whilst maintaining thetemperature below −25° C. After allowing to warm to −15° C. over 1 houra solution of zinc chloride in tetrahydrofuran (2.8 mL, 0.5M) was added,maintaining the temperature below −10° C. After 30 minutes the reactionmixture was treated with tetrakis(triphenylphosphine)palladium [0] (54mg) and 3-bromo-5-methoxy-indole-1-carboxylic acid tert-butyl ester(Reference Example 11(a), 152 mg) and stirred at 60° C. for 16 hours,then treated with water (30 mL). The mixture was extracted with ethylacetate (3×25 mL). The combined organics were washed with brine (2×15mL), dried over magnesium sulfate and then evaporated. The residue wassubjected to flash chromatography on silica eluting with a mixture ofethyl acetate and pentane (1:1, v/v) to give the title compound (45 mg)as a white foam. TLC R_(F)=0.34 (ethyl acetate/pentane: 1/1). HPLC(METHOD A): R_(T)=9.72 minutes.

REFERENCE EXAMPLE 41

[0839] 4-Methoxy-1-(1-toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine

[0840] A mixture of4-nitro-1-(1-toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine [ReferenceExample 9(b), 0.77 g] and dry dimethylformamide (25 mL) was treated withsodium methoxide (0.17 g) and stirred at 50° C. for 16 hours. A furtherportion of sodium methoxide (0.085 g) was then added and stirringcontinued for 8 hours, then the dimethylformamide was removed in vacuo.The residue was dissolved in ethyl acetate (100 mL) and washed with awater/brine mixture (1/1, 60 mL). The organics were dried over magnesiumsulfate and then evaporated. The residue was subjected to flashchromatography on silica eluting with ethyl acetate to give the titlecompound as a cream solid. HPLC: R_(T)=9.73 minutes. ¹H NMR [(CD₃)₂SO]:δ 8.22 (1H, d, J=8.2 Hz); 7.96 (2H, d, J=9.4 Hz); 7.71 (1H, d, J=3.5Hz); 7.39 (2H, d, J=9.4 Hz); 6.89 (1H, d, J=8.2 Hz); 6.72 (1H, d, J=3.5Hz); 3.93 (3H, s); 2.30 (3H, s).

REFERENCE EXAMPLE 42

[0841] 4-Phenyl-1H-pyrrolo[2,3-b]pyridine

[0842] A suspension of1-(2,6-dimethyl-1,4-dihydropyridin-4-one)-1H-pyrrolo[2,3-b]pyridiniumtetrafluoroborate (Reference Example 43, 1.0 g) in tetrahydrofuran (100mL) was treated with a solution of phenylmagnesium bromide intetrahydrofuran (9.6 mL, 1M) and stirred at room temperature for 72hours before adding water ((100 mL) and the tetrahydrofuran removed invacuo. The residue was extracted with chloroform (3×100 mL), and thecombined organics dried over sodium sulphate and evaporated. The residuewas subjected to flash chromatography on silica eluting with a mixtureof dichloromethane and methanol (99:1 v/v) to give the title compound(83 mg) as a white solid. MS: 195 (MH⁺). ¹H NMR [(CD₃)₂SO]: δ 8.27 (1H,d, J=4.1 Hz); 7.78 (2H, d, J=8.2 Hz); 7.57 (3H, m); 7.48 (1H, t, J=8.2Hz); 7.19 (1H, d, J=3.5 Hz); 6.60 (1H, s).

REFERENCE EXAMPLE 43

[0843]1-(2,6-Dimethyl-1,4-dihydropyridin-4-one)-1H-pyrrolo[2,3-b]pyridiniumTetrafluoroborate

[0844] A mixture of ethyl O-2,4,6-trimethylsulfonylacetohydroxamate(28.5 g) in perchloric acid (160 mL, 70%) was stirred at roomtemperature for 2 hours, then dichloromethane (30 mL) was added. Themixture was poured onto ice/water (1 litre) and rapidly extracted threetimes with dichloromethane (100 mL). The combined organics were washedtwice with brine (100 mL) and dried over sodium sulfate. The organicswere then added slowly to a solution of 1H-pyrrolo[2,3-b]pyridine (11.8g) in dichloromethane (100 mL). Filtration gave1-amino-1H-pyrrolo[2,3-b]pyridinium 2,4,6-trimethylphenylsulfonate,which was used directly in the next step.

[0845] A mixture of 1-amino-1H-pyrrolo[2,3-b]pyridinium2,4,6-trimethylphenylsulfonate (16.6 g) and3-acetyl-6-methyl-2H-pyran-2,4(3H)-dione (8.8 g) in concentratedhydrochloric acid (40 mL) was stirred at reflux for 4 hours, then cooledand concentrated in vacuo. The residue was dissolved in ethanol (30 mL)and diluted with a solution of tetrafluoroboric acid in diethyl ether(54% v/v, 30 mL) and stirred for 1 hour at room temperature. Filtrationgave the title compound (15.0 g) as a white solid, m.p. 247-248° C. ¹HNMR [(CD₃)₂SO]: 9.24 (1H, d, J=7.5 Hz); 9.13 (1H, d, J=7.5 Hz); 8.08(1H, d, J=4.2 Hz); 7.93 (1H, t, J=7.5 Hz); 7.22 (1H, d, J=4.2 Hz); 6.83(2H, s); 1.96 (6H, s).

REFERENCE EXAMPLE 44

[0846] (a) Dimethyl3-[6-(4-tert-butylphenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propionic1,1-diacid1,1-dicarboxylate

[0847] To a solution of dimethyl malonate (1.3 g) dissolved inN-methylpyrrolidinone (30 mL) at 0° C. under nitrogen was added sodiumhydride (0.39 g). After 10 minutes, a solution of[6-(4-tert-butylphenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl]methyltrimethylammonium iodide [1.12 g, Reference Example 45(a)] wasadded and the reaction mixture was warmed to room temperature andallowed to stir for 3 hours. The reaction mixture was poured into water(200 mL) and extracted three times with ethyl acetate (100 mL). Thecombined organic fractions were dried over magnesium sulfate and thenevaporated. The residue was subjected to flash column chromatography onsilica eluting with a mixture of ethyl acetate and pentane (1:1, v/v) togive the title compound (0.5 g) as a white solid.

[0848]¹H NMR(CDCl₃): δ 9.48 (1H, s); 8.42 (1H, s); 8.16 (1H, s); 7.64(2H, d, J=9.0 Hz); 7.58 (2H, d, J=9.0 Hz); 4.45 (1H, t, J=8.2 Hz); 3.63(2H, d, J=8.2 Hz); 3.58 (6H, s); 1.40 (9H, s).

[0849] (b) By proceeding in a manner similar to Reference Example 44(a)above but using[6-(4-(1-methyl)ethoxy)phenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl]methyltrimethylammonium iodide [Reference Example 45(b)], there was prepared dimethyl3-[6-(4-(1-methyl)ethoxyphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propionic1,1-diacid 1,1-dicarboxylate as a beige solid. MS:398 (MH⁺). ¹HNMR[CDCl₃]: δ 10.1(broad s, 1H); 8.41(d, 1H, J=2.3 Hz); 8.16(d, 1H,J=2.3 Hz); 7.62(d, 2H, J=8.21 Hz); 7.03(d, 2H, J=8.20 Hz); 4.64(m, 1H);4.45(t, 1H); 3.78(d, 1H); 3.60(s, 6H); 1.41(d, 6H, J=4.41 Hz).

[0850] (c) By proceeding in a manner similar to Reference Example 44(a)above but using[6-(4-fluorophenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]methyltrimethylammoniumiodide [Reference Example 45 (c)], there was prepared dimethyl3-[6-(4-fluorophenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propionic1,1-diacid 1,1-dicarboxylate as an off-white solid. NMR DMSO 12.2 (s,1H), 8.4 (d, 1H), 8.2 (d, 1H), 7.8 (d, 2H), 7.4 (d, 2H), 4.4 (t, 1H) 3.7(s, 6H), 3.6 (d, 2H). MS: 357 (MH⁺).

[0851] (d) By proceeding in a manner similar to Reference 44(a) abovebut using[6-(4-methoxyphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]methyltrimethylammoniumiodide [Reference Example 45 (d)], there was prepared dimethyl3-[6-(4-methoxyphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propionic1,1-diacid 1,1-dicarboxylate as an off-white solid. MS: 369 (MH⁺).

REFERENCE EXAMPLE 45

[0852] (a)[6-(4-tert-Butylphenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl]methyltrimethylammoniumIodide

[0853] To a solution of[6-(4-tert-butylphenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl]methyldimethylamine[0.8 g. Reference Example 46(a)] in tetrahydrofuran (50 mL) undernitrogen at 40 C. was added methyl iodide (4.5 mL). The reaction mixturewas stirred for 4 hours and the solvent was evaporated. The residue waschased with toluene (30 mL) and dried under vacuum to afford the titlecompound as a yellow solid which was used immediately without furtherpurification in the next reaction.

[0854] (b) By proceeding in a manner similar to Reference Example 45(a)above but using6-(4-(1-methyl)ethoxy)phenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl]methyldimethylamine [Reference Example 46(b)], there was prepared[6-(4-(1-methyl)ethoxy)phenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl]methyltrimethylammoniumiodide as a beige solid, which was used immediately without furtherpurification.

[0855] (c) By proceeding in a manner similar to Reference Example 45 (a)above but using[6-(4-fluorophenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl]methyldimethylamine[Reference Example 46 (c)], there was prepared6-(4-fluorophenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]methyltrimethylammoniumiodide as a yellow solid. ¹H NMR [(CD₃)₂SO]: δ 13.0 (s, 1H), 8.5 (d,1H), 8.4 (d, 1H), 7.7 (d, 2H), 7.6 (d, 2H), 3.1 (d, 2H), 2.9 (s, 9H).MS: 285 (MH⁺).

[0856] (d) By proceeding in a manner similar to Reference Example 45 (a)above but using[6-(4-methoxyphenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl]methyldimethylamine[Reference Example 46 (d)], there was prepared6-(4-methoxyphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]methyltrimethylammoniumiodide as an off-white solid. MS: 297 (MH⁺).

REFERENCE EXAMPLE 46

[0857] (a) [6-(4-tert-Butylphenyl-5H-pyrrolo[2,3-bpyrazin-7-yl]methyldimethylamine

[0858] To a solution of dimethylamine (15 mL of a 2M solution intetrahydrofuran) and acetic acid (0.45 mL) at 0 C. was addedformaldehyde (2.25 mL of a 40% aqueous solution). The reaction mixturewas stirred for 10 minutes. A solution of6-(4-tert-butylphenyl)-5H-pyrrolo[2,3-b]pyrazine [6.9 g, Example 1(w)]in tetrahydrofuran (400 mL) was added and the reaction mixture allowedto stir at room temperature overnight. The reaction mixture was washedwith IN sodium hydroxide solution, brine, dried over magnesium sulfateand evaporated in vacuo. The residue was subjected to flash columnchromatography on silica eluting with a mixture of tetrahydrofuran andmethanol (1:1, v/v) to give the title compound (0.8 g) as a yellowsolid. MS: 309 (MH⁺). HPLC (Method A): R_(T)=1.93 minutes.

[0859] (b) By proceeding in a manner similar to Reference Example 46(a)above but using 6-[4-(1-methyl)ethoxyphenyl]-5H-pyrrolo[2,3-b]pyrazine[Example 1(aa)], there was prepared6-(4-(1-methyl)ethoxy)phenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl]methyl-dimethylamineas a beige solid.

[0860] (c) By proceeding in a manner similar to Reference Example 46 (a)above but using 6-(4-fluorophenyl)-5H-pyrrolo[2,3-b]pyrazine [Example 1(ae)], there was prepared[6-(4-fluorophenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl]methyldimethylamine asan off-white solid. ¹H NMR [(CD₃)₂SO]: δ 12.0 (s, 1H), 8.5 (d, 1H), 8.2(d, 1H), 7.7 (d, 2H), 7.6 (d, 2H), 3.9 (d, 2H), 2.9 (s, 6H). MS: 270(MH⁺).

[0861] (d) By proceeding in a manner similar to Reference Example 46 (a)above but using 6-(4-methoxyphenyl)-5H-pyrrolo[2,3-b]pyrazine [Example1(af)], there was prepared[6-(4-methoxyphenyl-5H-pyrrolo[2,3-b]pyrazin-7-yl]methyldimethylamine asa off-white solid. MS: 282 (MH⁺).

REFERENCE EXAMPLE 47

[0862] Ethyl3-[2-dimethylamino-5-(5H-pyrrolo2,3-b]pyrazin-6-yl)phenyl]prop-2-enonate

[0863] To a solution of6-(4-amino-3-bromo)phenyl-5H-pyrrolo[2,3-b]pyrazine [0.1 g, ReferenceExample 48] in dry dimethylformamide (10 mL) in a schlenk tube was addedethyl acrylate (0.25 mL), palladium (II) acetate (0.05 g),tri-(2-methylphenyl)phosphine (0.07 g) and tributylamine (0.8 g). Thetube was sealed and heated at 95° C. for 24 hours then allowed to standat room temperature for a further 24 hours. The reaction mixture wasquenched with water (150 mL) and extracted into ethyl acetate (100 mL),washed with brine and dried over magnesium sulfate. After concentrationin vacuo the resultant orange gum was triturated with toluene to affordthe title compound as an orange solid (0.04 g). TLC: R_(F)=0.46 (ethylacetate). ¹H NMR [(CD₃)₂SO]: δ 12.40 (1H, s); 8.38 (1H, s); 8.34 (1H,s); 8.02 (1H, d, J=8.6 Hz); 7.89 (1H, d, J=16.5 Hz); 7.22 (1H, d, J=8.6Hz); 7.19 (1H, s); 6.81 91H, d, J=16.5 Hz); 4.23 (2H, q, J=7.1 Hz); 2.78(6H, s); 1.30 (3H, t, J=7.1 Hz).

REFERENCE EXAMPLE 48

[0864] 6-(3-Bromo-4-dimethylamino)phenyl-5H-pyrrolo[2,3-b]pyrazine

[0865] To a stirred solution of 4-(dimethylamino)benzonitrile (2.19 g)in chloroform (15 mL) was added pyridine (1.2 mL) and a solution ofbromine (0.75 mL) in chloroform (15 mL) dropwise over 45 minutes. Uponcomplete addition, the mixture was stirred for a further 30 minutes. Thereaction mixture was diluted with dichloromethane and washed with water,brine and evaporated to afford a yellow oil of3-bromo-4-dimethylaminobenzonitrile which was dissolved intetrahydrofuran (25 mL). Meanwhile, a stirred solution ofdiisopropylamine (2.7 mL) in tetrahydrofuran (50 mL), at −15° C. andunder nitrogen, was treated with a solution of n-butyllithium in hexanes(7.70 mL, 2.5M) over 30 minutes, whilst maintaining the temperaturebelow −10° C. After stirring for 30 minutes the mixture was treated withmethylpyrazine (1.21 g) over 15 minutes, then stirred for 1 hour. Thesolution of 3-bromo-4-(dimethylamino)benzonitrile was added over 1 hour,keeping the temperature below −10° C. The reaction mixture was allowedto warm to room temperature over 2 hours, then stood overnight, thentreated with water (10 mL). The tetrahydrofuran was removed in vacuo andthe resultant mixture was treated with a mixture of water and ethylacetate (1:1 v/v) and the mixture stirred for 15 minutes. The resultantprecipitate was collected by filtration and washed thoroughly withwater/ethyl acetate (1:1 v/v) to afford the title compound as a yellowsolid (1.0 g). TLC: R_(F)=0.41 (ethyl acetate).

REFERENCE EXAMPLE 49

[0866]6-(3-tert-Butyldimethylsilyloxy-4-methoxy)phenyl-5H-pyrrolo[2,3-b]pyrazine

[0867] A stirred solution of diisopropylamine (3.6 mL) intetrahydrofuran (133 mL), at −15° C. and under nitrogen, was treatedwith a solution of n-butyllithium in hexanes (11.21 mL, 2.5M) over 30minutes, whilst maintaining the temperature below −10° C. After stirringfor 30 minutes the mixture was treated with methylpyrazine (2.04 g) over15 minutes, then stirred for 1 hour and then treated with a solution of3-tert-butyldimethylsilyloxy-4-methoxybenzonitrile (5.7 g, ReferenceExample 50) in tetrahydrofuran (20 mL) over 1 hour, keeping thetemperature below −10° C. The reaction mixture was allowed to warm toroom temperature over 2 hours, then stood overnight, then treated withwater (10 mL). The tetrahydrofuran was removed in vacuo and theresultant mixture was partitioned between ethyl acetate and water. Thetwo layers were separated, and the aqueous layer was extracted withethyl acetate. The combined organics were dried over sodium sulfate andevaporated. The residue was subjected to flash chromatography on silicaeluting with a mixture of dichloromethane and methanol (32:1, v/v) togive the title compound (1.62 g) as a tan solid, which was used directlyin the next step. ¹H NMR [(CD₃)₂SO]: δ 8.12 (1H, s); 7.96 (1H, s); 7.44(1H, d, J=8.2 Hz); 7.33 (1H, s); 6.93 (1H, d, J=8.2 Hz); 6.84 (1H, s);3.63 (3H, s); 0.82 (9H, s); 0.01 (6H, s).

REFERENCE EXAMPLE 50

[0868] 3-tert-Butyldimethylsilyloxy-4-methoxy)benzonitrile

[0869] A solution of iso-vanillin (10.0 g) in dimethylformamide (100 mL)was treated with hydroxylamine hydrochloride (9.14 g) and heated underreflux for 1 hour. The dimethylformamide was removed under reducedpressure and the residue partitioned between ethyl acetate and water.The aqueous fraction was exhaustively extracted with ethyl acetate andthe combined organic fractions were dried over sodium sulfate andconcentrated in vacuo to afford a brown solid, which was dissolved intetrahydrofuran (200 mL). After treatment with sodium hydride (2.8 g),the reaction mixture was stirred at room temperature for 1 hour. Asolution of tert-butyldimethylsilyl chloride (10.9 g) in tetrahydrofuran(50 mL) was added and the mixture stirred under nitrogen overnight. Themixture was partitioned between water and diethyl ether. The organicextract was dried over sodium sulfate, concentrated in vacuo andsubjected to flash column chromatography on silica eluting with amixture of pentane and dichloromethane (1:3, v/v) to give the titlecompound (14.7 g) as a colourless oil which was used immediately in thenext reaction. ¹H NMR [(CD₃)₂SO]: δ 7.30 (1H, d, J=8.0 Hz); 7.11 (1H,s); 7.01 (1H, s); 3.70 (3H, s); 0.81 (9H, s); 0.01 (6H, s).

REFERENCE EXAMPLE 51

[0870] 4-(1-Methyl)ethoxybenzonitrile

[0871] A solution of 4-cyanobenzene (1 g) in hexamethylenetetramine (10mL) was stirred at ambient temperature until dissolution. 25% aqueoussodium hydroxide (2.7 mL) was then added and the resulting solutionstirred at ambient temperature for 30 minutes. 1-Methylethyl iodide(5.71 g) was added dropwise and the resulting solution stirred atambient temperature for 5 hours then poured into water (30 mL). Themixture was extracted three times with ethyl acetate (30 mL) and thecombined organic extracts were washed with water, then with brine, thendried over magnesium sulfate and then evaporated. The residue wassubjected to flash chromatography on silica eluting with a mixture ofethyl acetate and heptane (1:1, v/v) to give the title compound (1.2 g)as a white solid. MS: 162(MH⁺). ¹H NMR(CD₃)₂SO: δ:7.58(d, 2H, J=8.12Hz); 6.84(d, 2H, J=8.12 Hz); 4.62(m, 1H); 1.38(d, 6H, J=5.4 Hz).

REFERENCE EXAMPLE 52

[0872] 1H-5-Cyano-1-methyl-2-(methylthio)imidazole

[0873] A solution of1H-1-methyl-2-(methylthio)imidazole-5-carboxaldehyde (0.76 g) [ReferenceExample 53(a)] in dimethylformamide (15 mL) was treated withhydroxylamine hydrochloride (0.68 g). The mixture was refluxed for 4hours, cooled to ambient temperature and poured into water. Ethylacetate was added and the organic layer washed with water, brine, driedover magnesium sulfate and evaporated to give the title compound (0.47g) as a beige solid which was used without further purification,m.p.115° C. MS: 154 (MH⁺).

REFERENCE EXAMPLE 53

[0874] (a) 1H-1-Methyl-2-(methylthio) imidazole-5-carboxaldehyde

[0875] A stirred solution of1H-1-methyl-2-(methylthio)imidazol-5ylmethanol (8.1 g) [ReferenceExample 54] and manganese dioxide (28.97 g) in dichloromethane (160 mL)was refluxed for 7 hours. The reaction mixture was cooled to ambienttemperature and filtered through a pad of celite. The dichloromethanewas evaporated to give the title compound (6.61 g) as a yellow solid,which was used immediately in the next reaction.

[0876] (b) By proceeding in a manner similar to Reference Example 53(a)above but using 1-methyl-5-phenylpyrazol-3-ylmethanol [Reference Example66], there was prepared, 1-methyl-5-phenylpyrazole-3-carbaldehyde, m.p.106-108° C.

REFERENCE EXAMPLE 54

[0877] 1H-1-Methyl-2-(methylthio)imidazol-5ylmethanol

[0878] To a stirring suspension of1H-1-methyl-2-(thio)imidazol-5ylmethanol (5 g) [Reference example 55] inmethanol (500 mL) is added dropwise 1N sodium hydroxide solution (36 mL)at room temperature. The suspension was stirred at ambient temperaturefor 10 minutes. Iodomethane was added dropwise and stirring wascontinued for 12 hours. After evaporation of the methanol, the residuewas dissolved in dichloromethane and water was added. The organic layerwas washed with water, brine, dried over magnesium sulfate andevaporated. The residue was crystallized from ether to give the titlecompound (4.3 g) as a white solid, m.p. 51° C.

REFERENCE EXAMPLE 55

[0879] 1H-1-Methyl-2-(thio)imidazol-5ylmethanol

[0880] A mixture of 12.8 g of dihydroxyacetone dimer, 20.7 g ofpotassium thiocyanate and 12.4 g of methylamine was added to a solutionof 16 mL of acetic acid and 100 mL of butanol. The resulting whitemixture was stirred for 70 h after which it was suspended in 50 mL ofwater and filtered. The solid was washed with water (60 mL), thendiethyl ether (60 mL) and dried in vacuo to give the title compound (16g) as a white solid, m.p 204° C.

REFERENCE EXAMPLE 56

[0881] (a) 3-Cyano-1-methyl-1H-indazole

[0882] Sodium hydride (0.37 g, 60% dispersion in mineral oil) was addedto a solution of 3-cyano-1H-indazole (1.20 g, Reference Example 57) indry dimethylformamide (30 mL) under a nitrogen atmosphere at ambienttemperature. The mixture was allowed to stir for 1 hour then treatedwith methyl iodide (0.85 mL) and stirring was continued for 1 hour. Thereaction mixture was then poured into ice-water (15 mL). Theprecipitated solid was filtered then washed with water and then dried togive the title compound (0.80 g) as a beige solid, m.p.73° C. ¹H NMR[(CD₃)₂SO]: δ 7.91 (m, 2H); 7.60 (t, 1H); 7.42 (t, 1H); 4.21 (s, 3H).

[0883] (b) By proceeding in a manner similar to Reference Example 56(a)above but using 3-Cyano-4-phenyl-1H-pyrrole [Reference Example 58],there was prepared 3-cyano-1-methyl-4-phenyl-1H-pyrrole.

REFERENCE EXAMPLE 57

[0884] 3-Cyano-1H-indazole

[0885] A solution of o-aminobenzyl cyanide (0.5 g) in aqueoushydrochloric acid 1N (9.6 mL), was treated with a solution of aqueoussodium nitrite 1N (3.85 mL). After stirring at room temperature for 15minutes, the reaction mixture was filtered. The solid was recrystallisedfrom ethanol to give the title compound (0.4 g) as a yellow solid, m.p.138-140° C. ¹H NMR [(CD₃)₂SO]: δ 7.89 (d, 1H, J=7.7Hz); 7.76 (d, 1H,J=7.9Hz); 7.48 (t, 1H) ; 7.41 (t, 1H).

REFERENCE EXAMPLE 58

[0886] 3-Cyano-4-phenyl-1H-pyrrole

[0887] A solution of cinnamonitrile (16.53 g) and(para-toluenesulfonyl)methylisocyanide (25 g) in a mixture of ether anddimethyl sulphoxide (450 mL, 2:1) was added dropwise to a stirredsuspension of sodium hydride (6.14 g, 60% dispersion in mineral oil) inether (50 mL). An exothermic reaction took place. The reaction mixturewas then stirred at room temperature for 2 hours, then diluted withwater (500 mL) and this mixture was extracted three times with ether(250 mL). The combined extracts were washed with brine, then dried overmagnesium sulfate and then evaporated. The residue was subjected tofilter chromatography on a pad of silica eluting with a mixture of ethylacetate and pentane (1 L, 1:4, v/v) and then with a mixture of ethylacetate and pentane (2 L, 2:3, v/v). Fractions containing the requiredmaterial were evaporated and the residue was suspended in pentane (500mL) with stirring, then filtered to give the title compound as a solid,m.p. 120-122° C. MS: 167 (MH⁻).

REFERENCE EXAMPLE 59

[0888] 4-Pyrazinyl-1-butene

[0889] A solution of lithium diisopropylamine [prepared from a solutionof butyl lithium in hexanes (100 mL, 2.5M) and diispropylamine (25.3 g)at −35° C.] was treated with a solution of 2-methylpyrazine (23.5 g) indry tetrahydrofuran (300 mL) at −20° C. The mixture was stirred at −20°C. for 1 hour then cooled to −78° C. and treated with a solution ofallyl bromide (30.8 g) in dry tetrahydrofuran (300 mL). This mixture waswarned to room temperature and stirred at this temperature for 2 hoursthen left overnight and then treated with saturated ammonium chloridesolution (50 mL) followed by water (200 mL). The mixture was thenextracted twice with ether (200 mL). The combined extracts were driedover magnesium sulfate then evaporated. The residue was distilled togive the title compound (22 g) as a colorless oil, b.p. 70° C./1 mm Hg.

REFERENCE EXAMPLE 60

[0890]2-[5-(pyridin-4-yl)-1-methyl-1H-indol-3-yl]-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine

[0891] A mixture of2-[5-(1-benzyloxycarbonyl-1,2,5,6-tetrahydropyridin-4-yl)-1-methyl-1H-indol-3-yl]-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine(1.7 g, Reference Example 61) ethanol (53 mL) and palladium on carbon(0.35 g) was stirred in the presence of hydrogen for 4 hours, then leftstanding at room temperature overnight. After a further day a furtherquantity of palladium on carbon (0.18 g, 10%) was added and stirring wascontinued in the presence of hydrogen for a further 8 hours. Afterstanding at room temperature for 4 days the reaction mixture wasfiltered through Hyflo and the filter pad was washed well with ethanol.The combined filtrate and washings was treated with palladium on carbon(0.35 g) and the mixture was stirred in the presence of hydrogen. Themixture was filtered through Hyflo and the filter pad was washed wellwith ethanol. The combined filtrate and washings was evaporated and theresidue was subjected to flash chromatography on silica eluting with amixture of ethyl acetate and pentane (4:1, v/v) to give the titlecompound as a light brown solid, m.p. 82-85° C.

REFERENCE EXAMPLE 61

[0892]2-[5-(1-benzyloxycarbonyl-1,2,5,6-tetrahydropyridin-4-yl)-1-methyl-1H-indol-3-yl]-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine

[0893] A mixture of benzyl1-[3,6-dihydro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl](2H)pyridinecarboxylate(2 g, prepared according to the procedure described by P. Eastwood,Tetrahedron Letters, 2000, 41, pages 3705-3708),dichloro[1,1′-bis(diphenylphosphino)-ferrocene]palladium[II] (0.25 g,)and potassium carbonate (2.42 g), under nitrogen, was treated with asolution of trifluoro-methanesulfonic acid1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-ylester [1.6 g, Reference Example 18(a)] in dimethylformamide(76 mL). Themixture was heated at 80° C. for 4 hours (tlc indicated that startingmaterial was still present), then treated with a further quantity oftrifluoromethanesulfonic acid1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-ylester (0.15 g), then heated at reflux temperature for 4 hours and thenleft at room temperature overnight. A further quantity oftrifluoro-methanesulfonic acid1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-ylester [0.15 g, Reference Example 18(a)] was added and the mixture washeated at reflux temperature for a further 4 hours then evaporated. Theresidue was partitioned between ethyl acetate and water, and the aqueouslayer was extracted three times with ethyl acetate (50 mL). The combinedorganic phases were washed with brine, then dried over magnesium sulfateand then evaporated. The residue was subjected to flash chromatographyon silica eluting with a mixture of ethyl acetate and pentane (1:1, v/v)to give the title compound as a light brown viscous liquid which wasused without further purification.

REFERENCE EXAMPLE 62

[0894] (a)2-Iodo-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile

[0895] A stirred solution of diisopropylamine (0.38 mL) intetrahydrofuran (7 mL), at −70° C. and under nitrogen, was treated witha solution of n-butyllithium in hexanes (1.06 mL, 2.5M) over 5 minutes,whilst maintaining the temperature below −65° C. After stirring for 20minutes the mixture was added, at −70° C., to a solution of1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile (0.65 g,Reference Example 63) in tetrahydrofuran (15 mL) and stirred at −70° C.for 45 minutes. A solution of iodine (0.9 g) in tetrahydrofuran (10 mL)was then added at −70° C. The reaction mixture was allowed to warm up toroom temperature over 1 hour, and stirred for 18 hours, then treatedwith water (10 mL). The reaction mixture was evaporated in vacuo and theresidue partitioned between ethyl acetate (75 mL) and water (50 mL). Theinsoluble material was filtered, washed with ether and dried in vacuo togive the title compound (0.45 g) as a white solid. The filtrate wasseparated and the organics washed sequentially with saturated sodiumthiosulphate solution (2×30 mL), water (30 mL) and brine (30 mL), driedover sodium sulphate and evaporated. The residue was triturated withdiethyl ether to give the title compound (0.25 g) as a cream solid. TLCR_(F)=0.43 (ethyl acetate/heptane 1:1). MS: 424 (MH⁺).

[0896] (b) By proceeding in a similar manner to Reference Example 62(a)but using 4-chloro-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[Reference Example 9(c)], there was prepared4-chloro-2-iodo-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine as anoff white foam. MS: 432 (MH⁺). ¹H NMR (CDCl₃): δ 8.25 (d, 1H), 8.05 (d,2H), 7.3 (d, 2H), 7.15 (d, 1H), 7.1 (s, 1H), 2.4 (s,3H)

[0897] (c) By proceeding in a similar manner to Reference Example 62(a)but using 5-phenyl-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[Reference Example 67], there was prepared2-iodo-5-phenyl-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine as alight brown solid.

[0898] (d) By proceeding in a similar manner to Reference Example 62(a)but using 4-phenyl-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine[Reference Example 9(e)], there was prepared the2-iodo-4-phenyl-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine as awhite solid. ¹H NMR [(CD₃)₂SO]; δ 8.43 (1H, d, J=4.5Hz); 8.04 (2H, d,J=8.2Hz); 7.98 (1H, d, J=4.5Hz); 7.69 (2H, dd, J=7.2, 1.9Hz); 7.56 (2H,tt, J=7.2, 1.9Hz); 7.44 (2H, d, J=8.2Hz); 7.42 (1H, d, J=5.0 Hz), 6.92(1H, d, J=4.0 Hz), which was used without further purification.

REFERENCE EXAMPLE 63

[0899] 1-(Toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile

[0900] A mixture of1-(2,6-dimethyl-1,4-dihydropyridin-4-one)-1H-pyrrolo[2,3-b]pyridiniumtetrafluoroborate (Reference Example 43, 5.0 g) and water (80 mL) wastreated with a saturated aqueous solution of potassium cyanide (25 mL)and stirred at room temperature for 48 hours. A solution oftoluene-4-sulfonyl chloride (2.9 g) in toluene (100 mL), a solution ofsodium hydroxide (4.0 g) in water (10 mL) and tetrabutylammoniumhydrogen sulphate (0.05 g) were added and stirred at room temperature 72hours. The mixture was filtered through Celite and partitioned. Theaqueous was extracted three times with ethyl acetate (50 mL) and thecombined organics were washed with water (50 mL), brine (50 mL), driedover magnesium sulphate and evaporated in vacuo. The residue wassubjected to flash chromatography on silica eluting with a mixture ofethyl acetate and heptane (3/7, v/v) to give the title compound (1.1 g)as a white solid, TLC: R_(F)=0.60 (ethyl acetate/heptane, 3:7); ¹H NMR[(CD₃)₂SO]: 8.54 (1H, d, J=4.7 Hz); 8.08 (2H, d, J=8.2 Hz); 7.95 (1H, d,J=3.6 Hz); 7.44 (1H, d, J=4.3 Hz); 7.31 (2H, d, J=8.2 Hz); 6.82 (1H, d,J=3.3 Hz); 2.39 (3H, s); and 1H-pyrrolo[2,3-b]pyridine-4-carbonitrile(0.13 g) as a white solid, TLC R_(F)=0.24 (ethyl acetate/heptane 3:7);¹H NMR [(CD₃)₂SO]: δ 10.19 (1H, s); 8.44 (1H, d, J=4.6 Hz); 7.59 (1H,m); 7.40 (1H, d, J=4.6 Hz), 6.78 (1H, m).

REFERENCE EXAMPLE 64

[0901] 4-Chloro-1H-pyrrolo[2,3-b]pyridine

[0902] 1H-Pyrrolo[2,3-b]pyridine-N-oxide (Reference Example 65) (10.0 g)in phosphorous oxychloride (75 mL) was heated at reflux for 8 hours. Theexcess phosphorous oxychloride was evaporated and the residue was takenup in water and the solution was brought to a pH=8-9, the resultantprecipitate was filtered and air-dried to give the title compound as anoff-white solid (10.2 g). MS: 152 (MH⁺). ¹H NMR (CDCl₃): δ 8.2 (d, 1H),7.5 (d,,1H), 7.2 (d, 2H), 6.6 (d, 2H).

REFERENCE EXAMPLE 65

[0903] 1H-Pyrrolo[2,3-b]pyridine-7-oxide

[0904] A solution of 3-chloroperbenzoic acid (224.3 g) indichloromethane (1500 mL) was cooled to 0° C. To this a solution of1H-pyrrolo[2,3-b]pyridine (59.1 g) in dichloromethane (500 mL) was addeddropwise over 30 minutes. The reaction mixture was stirred at roomtemperature for 1 hour. The solution was concentrated, diluted withmethanol (1500 mL) and treated with 10% potassium carbonate in water(300 mL). The slurry was filtered and the filtrate was evaporated todryness. The residue was chromatographed on neutral alumina with 20%methanol in dichloromethane to give the title compound as a tan solid(47.0 g). MS: 135 (MH⁺). ¹HNMR (CDCl₃): δ 13.1 (s, 1H), 8.2 (d,1H), 7.65(d, 1H), 7.4 (d, 1H), 7.0 (m, 1H), 6.55 (d, 1H).

REFERENCE EXAMPLE 66

[0905] 1-Methyl-5-phenylpyrazol-3-ylmethanol

[0906] A stirred suspension of sodium borohydride (1.28 g) in drytetrahydrofuran (80 mL) was treated with calcium chloride (1.88 g). Themixture was stirred for 1 hour then treated with a solution of ethyl1-methyl-5-phenylpyrazol-3-ylcarboxylate (5.2 g, prepared according tothe procedure described by Martins et al., J. Heterocycl. Chem. (1999),36(1), 217-220) in dry tetrahydrofuran (40 mL). After stirring at roomtemperature for 3 days and at reflux temperature for 8 hours the mixturewas treated with sodium hydroxide solution (50 mL, 1N). This mixture wasstirred at room temperature for 1 hour, then evaporated to remove theorganic solvents and then extracted three times with dichloromethane(140 mL). The combined extracts were washed with water, then dried overmagnesium sulfate and then evaporated to give the title compound as awhite solid, m.p. 95-99° C.

REFERENCE EXAMPLE 67

[0907] 5-Phenyl-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine

[0908] A mixture of phenyl boronic acid (1.74 g),5-bromo-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine [5 g, ReferenceExample 9(d)], (tetrakis)tripyhenylphosphine palladium[0] (0.49 g) andsaturated aqueous sodium bicarbonate solution (133 mL) anddimethylformamide (266 mL), under nitrogen, was heated at refluxtemperature overnight. The reaction mixture was filtered through Hyfloand then evaporated. The residue was partitioned between ethyl acetate(50 mL) and water (25 mL) and the aqueous layer was extracted with ethylacetate (25 mL). The combined organic phases were washed with water (25mL), then with brine (20 mL), then dried over magnesium sulfate and thenevaporated. The residue subjected to chromatography on silica elutingwith a mixture of pentane and ether (1;1, v/v) to give the titlecompound as a white solid, mp. 151-152° C. MS: 335 (MH⁺).

IN VITRO TEST PROCEDURES

[0909] A. In Vitro Test Procedures for Syk

[0910] 1. Inhibitory Effects of Compounds on Syk Kinase

[0911] Inhibitory effects of compounds on Syk kinase were determinedusing a time-resolved fluorescent assay.

[0912] The catalytic domain of Syk kinase (residues A340-N635 ) wasexpressed as a fusion protein in yeast cells and purified tohomogeneity. Kinase activity was determined in 50 mM Tris-HCl buffer pH7.0 containing 50 mM NaCl, 5 mM MgCl₂, 5 mM MnCl₂, 1 μM adenosinetriphosphate and 10 μM synthetic peptideBiotin-(β-Alanine)₃-DEEDYEIPP-NH₂. Enzyme reactions were terminated bythe addition of buffer containing 0.4M KF, 133 mM EDTA, pH 7.0,containing a streptavidin-XL665 conjugate and a monoclonalphosphospecfic antibody conjugated to a europium cryptate (Eu—K).Features of the two fluorophores, XL-665 and Eu—K are given in G. Mathiset al., Anticancer Research, 1997, 17, pages 3011-3014. The specificlong time signal of XL-665, produced only when the synthetic peptide isphosphorylated by Syk, was measured on a Packard Discovery Microplateanalyzer. Inhibition of syk activity with compounds of the invention wasexpressed as percentage inhibition of control activity exhibited in theabsence of test compounds. Particular compounds of the invention inhibitsyk activity with IC₅₀s in the range 100 micromolar to 10 nanomolar.Preferred compounds of the invention inhibit syk activity with IC₅₀s inthe range 100 nanomolar to 10 nanomolar.

[0913] 2. Antigen-induced Degranulation of Rat Bosophilic Leukemia (RBL)Cells as Measured by [³H] 5-hydoxytryptamine (Serotonin) Release

[0914] 2.1 Cell Culture, Labelling of RBL-2H3 Cells and Performance ofAssay.

[0915] For each 24-well culture plate to be set up, 6×10⁶ cells RBL-2H3cells were washed and resuspended in 15 mL DMEM-10 containing 25 μl of 1mCi/ mL [³H]-serotonin (0.5 μCi/mL final concentration) and 1 μg/mL (15mL) of anti-DNP IgE. 0.5 mL of cell suspension was added into each wellof a 24-well plate. Cells were incubated for 2 days at 37° C., untilthey have reached confluence. The medium was gently aspirated from eachwell and the cells were then washed with assay buffer. A final volume of200 mL of assay buffer (+or − the test compounds at the appropriateconcentrations) was then added to each of three replicate wells. 100ng/mL of DNP (antigen) was then added to all wells (excluding negativecontrol wells i.e. to measure spontaneous [³H]-serotonin release in theabsence of receptor cross-linking). The cells were incubated for 30minutes at 37° C. and the reaction was stopped by transferring 100 μl ofthe supernatant from each sample into a liquid scintillation microtitreplate kept on ice. 200 μl of scintillant-40 was then added to each wellof the microtitre plate and the plate was read on a Topcount LiquidScintillation Counter.

[0916] 2.2 Calculation of Results

[0917] (i) The mean±s.e.m. of each set of triplicate wells wascalculated.

[0918] (ii) Maximum response was the positive control wells containingantigen (10 ng/mL) but no compound.

[0919] (iii) Minimum response was the control wells containing noantigen and no compound.

[0920] (iv) Using these values as the maximum (100%) and minimum (0%)values respectively, the data was normalised to give a percentage of themaximum response.

[0921] (v) A dose response curve was plotted and the IC₅₀ of thecompound was calculated.

[0922] Compounds of the invention inhibit antigen-induced degranulationof Rat Bosophilic leukemia (RBL) cells with EC₅₀s in the range 100micromolar to 0.01 micromolar.

[0923] B. In Vitro Test Procedures for KDR

[0924] 1. Inhibitory Effects of Compounds on KDR

[0925] Inhibitory effects of compounds on KDR-substrate phosphorylationassay—were determined using a flashplate (96-multiwell plates, NewEngland Nuclear) assay.

[0926] The cytroplasmic domain of human enzyme has been cloned asglutathione S-transferase (GST) fusion into the pFastBac-GST tagged(reading frame) B baculovirus expression vector. The protein has beenexpressed in SF21 cells and purified to about 60% homogeneity.

[0927] Kinase activity was determined in 20 mM4-morpholinepropanesulfonic acid sodium salt, 10 mM MgCl₂, 10 mM MnCl₂,1 mM Dithiothreitol, 2.5 mM ethyleneglycol-bis(beta-aminoethylether)-N,N′-tetraacetic acid, 10 mM β-glycerophosphate,pH 7.2 containing 10 mM MgCl₂, 100 μM Na₃VO₄, 1 mM NaF. 10 μl ofcompound were added to 70 μl of kinase buffer containing 100 ng ofKinase Domain Receptor (KDR) enzyme at 4° C. Reaction was started byaddition of 20 μl of solution containing 2 μg of substrate (SH2-SH3fragment of PLCγ expressed as GST fusion protein), 2 μCi γ³³P[ATP] and 2μM cold ATP. After 1 h incubation at 37° C., reaction was stopped byaddition of 1 volume (100 μl) of 200 mM EDTA. The assay buffer was thendiscarded and the wells washed three fold with 300 μl of phosphatebuffered saline. Radioactivity was measured in each well using a PackardModel Top Count NXT instrument.

[0928] Background signal was deduced from the measurement ofradioactivity in quadruplate wells containing radioactive ATP andsubstrate alone in kinase buffer.

[0929] Control activity was deduced from the measurement ofradioactivity of quadruplate wells containing the complete assaycocktail (γ³³P-[ATP], KDR and PLCg substrate) in the absence of testcompound.

[0930] Inhibition of KDR activity with compound of the invention wasexpressed as percentage inhibition of control activity exhibited in theabsence of test compound.

[0931] SU5614 1 μM (Calbiochem) was included in each plate inquadruplate as a control of inhibition.

[0932] IC₅₀'s were calculated for compounds of the invention by plottinga dose-response curve. IC₅₀ corresponded to the concentration ofcompound of the invention that induced a 50% inhibition of kinaseactivity.

[0933] Particular compounds of the invention inhibit KDR activity withIC₅₀s in the range 100 micromolar to 0.3 micromolar.

[0934] 2. Cellular Activity on Endothelial Cell

[0935] 2.1 Inhibition of Vascular Endothelial Growth Factor(VEGF)-dependent Human Dermal Microvascular Endothelial Cells (HDMEC)Proliferation.

[0936] The anti-KDR activity of the molecules of the invention wasevaluated by [¹⁴C]-thymidine uptake on HDMEC (Human Dermal MicrovascularEndothelial Cell) in response to VEGF. HDMEC (Promocell, passage 5 to 7)were seeded in 100 μl at 5,000 cells per well in Cytostar 96-multiwellplates (Amersham) precoated with Attachment factor (AF, CascadBiologics) at 37° C., 5% CO₂, at day 1. On day 2, complete cell medium(Basal medium supplemented with 5% of Fetal calf serum (FCS) andcocktail of growth factors) was replaced by minimum medium (basal mediumsupplemented with 5% of FCS) and cells were incubated for another 24 h.On day 3, medium was replaced by 200 μl of fresh minimum mediumsupplemented or not with 100 ng/ml VEGF (R&D System) and containing ornot compounds of the invention and 0.1 μCi [¹⁴C]-thymidine. Cells wereincubated at 37° C., 5% CO₂ for 4 days. [¹⁴C]-thymidine uptake was thenquantified by counting the radioactivity. Assays were performed in threereplicate wells. The final concentration of DMSO in the assay is 0.1%.The % inhibition is calculated as[cpm_((+VEGF))−cpm_((+VEGF+cpd))/cpm_((+VEGF))−cpm_((BM5%FCS))]×100.

[0937] 2.2 Effect of Molecules on VEGF-independent HDMEC Growth:

[0938] HDMEC (5,000 cells per well) are seeded in complete medium (CM)in Cytostar 96-multiwell plates (Amersham) precoated with Attachmentfactor (AF, Cascad Biologics) at 37° C., 5% CO₂, at day 1. Completemedium is then removed and cells are incubated in 200 μl of completemedium containing molecules of the invention and [¹⁴C]-thymidine (0.1μCi). The uptake of [¹⁴C]-thymidine is quantified using Wallac betaplateafter 3 days of incubation. The % inhibition is calculated as[cpm_((CM))−cpm_((CM+cpd))/cpm_((CM))]×100.

[0939] C. In Vitro Test Procedures for Aurora2

[0940] 1. Inhibitory Effects of Compounds on Aurora2 Kinase

[0941] Inhibitory effects of compounds on Aurora2 kinase were determinedusing a nichel-chelate flashplate radioactive assay.

[0942] N-terminally His-tagged full length recombinant aurora2 wasexpressed in E. coli and purified to near homogeneity.

[0943] N-terminally His-tagged NuMA (Nuclear protein that associateswith the Mitotic Apparatus) C-terminal fragment (Q1687-H2101) wasexpressed in E. coli, purified by nichel chelate chromatography and usedas substrate in Aurora2 kinase assay. For kinase activity determinationNuMAsubstrate was freshly equilibrated in kinase buffer (50 mM Tris-HCl,pH7.5, 50 mM NaCl, 10 mM MgCl₂) supplemented with 10% (v/v) glycerol and0.05% (w/v) NP40 by chromatography on a Pharmacia PD10 column.

[0944] The kinase activity of Aurora2 was measured in a nichel chelateflashplate (New England Nuclear, model SMP107). Each well contained 100μl of the following solution: 0.02 μM Aurora2; 0.5 μM NuMAsubstrate; 1μM ATP supplemented with 0.5 μCi[γ-³³P]-ATP. The solutions wereincubated for 30 minutes at 37° C. The assay buffer was then discardedand the wells rinsed twice with 300 μl of kinase buffer. Radioactivitywas measured in each well using a Packard Model Top Count NXTinstrument.

[0945] Background signal was deduced from the measurement ofradioactivity in duplicate wells containing radioactive ATP alone inkinase buffer treated in the same manner as other samples.

[0946] Control activity was deduced from the measurement ofradioactivity of duplicate wells containing the complete assay cocktail(ATP, Aurora2 and NuMA substrate) in the absence of test compound.

[0947] Inhibition of Aurora2 activity with compound of the invention wasexpressed as percentage inhibition of control activity exhibited in theabsence of test compound. Staurosporin was included in each plate as acontrol of inhibition.

[0948] IC₅₀'s were calculated for compounds of the invention by plottinga dose-response curve. IC₅₀ corresponded to the concentration ofcompound of the invention that induced a 50% inhibition of kinaseactivity.

[0949] Particular compounds of the invention inhibit Aurora2 activitywith IC₅₀s in the range 100 micromolar to 0.3 micromolar.

[0950] C. In Vitro Test Procedures for FAK

[0951] 1. Inhibitory Effects of Compounds on FAK

[0952] Inhibitory effects of compounds on FAK kinase—autophosphorylationassay—were determined using a time-resolved fluorescent assay.

[0953] The full length cDNA of human enzyme has been cloned into thepFastBac HTc baculovirus expression vector. The protein has beenexpressed and purified to about 70% homogeneity.

[0954] Kinase activity was determined in 50 mM Hepes pH 7.2 containing10 mM MgCl₂, 100 μM Na₃VO₄, 15 μM adenosine triphosphate. Enzymereactions were terminated by the addition of Hepes buffer pH 7.0,containing 0.4 M KF, 133 mM EDTA, BSA 0.1% containing an anti-6Hisantibody labelled with XL665 (FAK is His-tagged) and a monoclonaltyrosine phosphospecfic antibody conjugated to a europium cryptate(Eu—K). Features of the two fluorophores, XL-665 and Eu—K are given inG. Mathis et al., Anticancer Research, 1997, 17, pages 3011-3014. Thespecific long time signal of XL-665, produced only when the FAK enzymeis autophosphorylated, was measured on a Packard Discovery Microplateanalyzer. Inhibition of FAK activity with compounds of the invention wasexpressed as percentage inhibition of control activity exhibited in theabsence of test compounds.

[0955] 2. Proliferation/Viability of Human Melanoma SK-Mel-28 Cells asMeasured by [¹⁴C] Thymidine Uptake

[0956] 2.1 Cell Culture, Labelling of SK-Mel-28 Cells and Performance ofAssay.

[0957] SK-Mel-28 were seeded at 5,000 cells per well in Cytostar96-multiwell plates (Amersham) at 37° C., 5% CO₂, at day 1. On day 2,cell medium was replaced by fresh Eagle's minimum essential medium (MEM)culture medium supplemented with 10% FCS, 1% non essential amino acids,1% sodium pyruvate and containing 0.1 μCi of [¹⁴C]-Thymidine plusincreasing concentrations of compounds in a 200 μl final volume. Cellswere incubated at 37° C., 5% CO₂ for 48 hours. [¹⁴C]-Thymidine uptakewas quantified by counting the radioactivity 48 hours after initiationof treatment. Assays were performed in three replicate wells.

[0958] 2.2 Calculation of Results

[0959] (i) The mean±s.e.m. of each set of triplicate wells wascalculated.

[0960] (ii) Maximum response was the positive control wells containingcells but no compound.

[0961] (iii) Minimum response was the control wells containing no celland no compound.

[0962] (iv) Using these values as the maximum (100%) and minimum (0%)values respectively, the data were normalized to give a percentage ofthe maximum response.

[0963] (v) A dose response curve was plotted and the IC₅₀ (theconcentration of drug that induces a 50% decrease in [¹⁴C]-thymidineuptake) of the compound was calculated.

[0964] 3. Migration of Human Melanoma SK-Mel-28 Cells on FibronectinMatrix

[0965] 3.1 Cell Culture and Performance of Assay.

[0966] SK-Mel-28 (250,000 cells) were pretreated with increasingconcentrations of compounds for 15 min at 37° C., 5% CO₂. They were thenloaded in presence of the compound on the upper side of 12 μm12-multiwell chemotaxis Boyden chambers (Becton Dickinson) and allowedto migrate to the lower chamber containing fibronectin (10 μg/ml) aschemoattractant in basal RPMI culture medium for 24 hours at 37° C., 5%CO₂. Cells were then fixed and stained in Diff-Quick (Diff-Quick Fix, Iand II solutions, Dade Behring) and cells from the upper side of thechamber were removed. Stain was solubilized from lower side adherentcells and cell migration was quantified by optic density measurement.Assays were performed in two replicate wells.

[0967] 3.2 Calculation of Results

[0968] (i) The mean±s.e.m. of each set of duplicate wells wascalculated.

[0969] (ii) Maximum response was positive control wells containing cellsbut no compound and allowed to migrate on fibronectin.

[0970] (iii) Minimum response was the control wells containing cells butno compound and allowed to migrate on basal culture medium w/ochemoattractant.

[0971] (iv) Using these values as the maximum (100%) and minimum (0%)values respectively, the data were normalized to give a percentage ofthe maximum response.

[0972] (v) A dose response curve was plotted and the IC₅₀ (theconcentration of drug that induces a 50% decrease in cell migration) ofthe compound was calculated.

[0973] Particular compounds of the invention inhibit FAK activity withIC₅₀s in the range 100 micromolar to 0.3 micromolar.

IN VIVO TEST PROCEDURES

[0974] 1. Inhibition of Antigen Induced Airway Inflammation—Single- andMultiple-day Oral Dosing Studies.

[0975] Compounds of the invention were assessed in the allergic BrownNorway rat. The models used in these in vivo studies mimic relevantpathological features of allergic airway disease. These studiesdemonstrated that compounds of the invention inhibit the accumulation ofinflammatory cells in the airways allergic twenty-four hours afterantigen inhalation. The endpoints measured included the appearance ofinflammatory leukocytes in the bronchoalveolar lavage fluid (BALF), lungdigest fluid, and in the tissue as quantified by histopathologicalanalysis.

[0976] Protocol for Sensitization and Challenge

[0977] Brown Norway rats were sensitized on days 0, 12 and 21 withovalbumin (100 μg, i.p) administered with aluminum hydroxide (100 mg,i.p). On day 30, the rats were exposed to a 1% aerosol of ovalbumin fora period of 30 minutes. The animals were then returned to housing.

[0978] Protocol for Dosing

[0979] Test drug was administered orally 1 hour before the initiation ofthe allergen inhalation challenge. Four hours after the end of theantigen inhalation challenge, a second dose of drug was given orally.Doses of compound were administered at half log divisions between 3 and100 mg/kg.

[0980] In separate studies drug was administered two times daily for 4days before the inhalation of antigen. The final dose of compound inthese studies was also given at 4 hours after the antigen challenge.

[0981] Protocol for Bronchoalveolar Lavage (BAL) Recovery

[0982] Twenty-four hours after the antigen inhalation challenge, cellswere recovered from the airway lumen by bronchoalveolar lavage byeuthanizing the animals, and washing the lungs with three 5-ml aliquotsof RPMI/FCS. The washes were allowed to remain in the lungs for 30seconds each before gentile removal. The three samples were pooled andtotal and differential white blood cell counts were measured on BALsamples. An ARGOS system was used to assess total cells and differentialcell counts were made using light microscopy of Wright-Giemsa stainedcytocentrifuge preparations.

[0983] Protocol for Histopathology of Lungs

[0984] Immediately after BAL, the lungs were insufflated with 10%neutral buffered formalin (NBF), at 30 cm water pressure. The lungs wereremoved and placed in jars of 10% NBF. After fixation in 10% NBF for aminimum of 24 hours the lungs were processed through graded alcohol andinto wax locks. The lungs were blocked longitudinally and one 2 μmlongitudinal section for each animal was cut at the level of the mainbronchi. Sections were then stained with haematoxylin and eosin.Pathological assessment of sections was performed and a grading for thebronchiolar epithelium and sub-mucosa was assigned

[0985] Protocol for Lung Digest

[0986] In some studies the lug itself was digested, to recover theinflammatory cells localized within the tissue. In these studies thecells were obtained by perfusing the left lung with RPMI/FCS in order toremove the blood pool of cells immediately after BAL. In the se studiesthe he right hand side of the lung was insufflated and fixed withbuffered formalin for histopathological analysis. The lung to undergodigestion was standardized across animals by taking a 300 mg the sectionof the lung tissue and exposing it to collagenase digestion. This freedthe cells within the lung tissue and allowed their recovery. Total anddifferential cell counts were performed on these recovered cells.

[0987] Results

[0988] (i) Following antigen inhalation there was a significant increasein the numbers of eosinophils and neutrophils in the non-drug treatedgroups. His was evidenced by the significant increase in BAL and tissuedigest eosinophil and neutrophil numbers as well as the lunghistopathology score.

[0989] (ii) No changes in BAL macrophage/monocyte cell numbers wereobserved with antigen challenge or with any drug treatment.

[0990] (iii) The compound as able to inhibit significantly theinfiltration of neutrophils and eosinophils 24 hours after antigenicchallenge compared to the non-drug treated controls as assessed in allthree methods noted above. The dose range for efficacy was between 3 and100 mg/kg po.

[0991] (iv) In the multiple-day drug administration studies, there wasquantitatively similar inhibition of the cellular influx as seen in thesingle day studies.

[0992] These results indicate that compounds of the inventiondemonstrate anti-inflammatory activity when given prophylacticlly in arat model of antigen induced leukocyte infiltration

[0993] 2. Inhibition of Antigen Induced Airway Inflammation—Single-dayip Dosing Studies

[0994] Protocol for Sensitization and Challenge

[0995] Brown Norway rats were sensitized on days 0, 12 and 21 withovalbumin (100 μg, i.p) administered with aluminum hydroxide (100 mg,i.p). On day 30, the rats were exposed to a 1% aerosol of ovalbumin fora period of 30 minutes. The animals were then returned to housing.

[0996] Protocol for Dosing

[0997] Test drug was administered four times intraperitoneally ratherthan po. The dosing regimen was 30 min pre-challenge and 2, 4 and 8hours after allergen inhalation challenge.

[0998] Protocol for Bronchoalveolar Lavage (BAL) Recovery

[0999] Twenty-four hours after the antigen inhalation challenge, cellswere recovered from the airway lumen by bronchoalveolar lavage byeuthanizing the animals, and washing the lungs with three 5-ml aliquotsof RPMI/FCS. The washes were allowed to remain in the lungs for 30seconds each before gentile removal. The three samples were pooled andtotal and differential white blood cell counts were measured on BALsamples. An ARGOS system was used to assess total cells and differentialcell counts were made using light microscopy of Wright-Giemsa stainedcytocentrifuge preparations.

[1000] Protocol for Histopathology of Lungs

[1001] Immediately after BAL, the lungs were insufflated with 10%neutral buffered formalin (NBF), at 30 cm water pressure. The lungs wereremoved and placed in jars of 10% NBF. After fixation in 10% NBF for aminimum of 24 hours the lungs were processed through graded alcohol andinto wax locks. The lungs were blocked longitudinally and one 2 μmlongitudinal section for each animal was cut at the level of the mainbronchi. Sections were then stained with haematoxylin and eosin.Pathological assessment of sections was performed and a grading for thebronchiolar epithelium and sub-mucosa was assigned

[1002] Protocol for Lung Digest

[1003] In some studies the lug itself was digested, to recover theinflammatory cells localized within the tissue. In these studies thecells were obtained by perfusing the left lung with RPMI/FCS in order toremove the blood pool of cells immediately after BAL. In the se studiesthe he right hand side of the lung was insufflated and fixed withbuffered formalin for histopathological analysis. The lung to undergodigestion was standardized across animals by taking a 300 mg the sectionof the lung tissue and exposing it to collagenase digestion. This freedthe cells within the lung tissue and allowed their recovery. Total anddifferential cell counts were performed on these recovered cells.

[1004] Results

[1005] (i) Following antigen inhalation there was a significant increasein the numbers of eosinophils and neutrophils in the non-drug treatedgroups. This was evidenced by the significant increase in BAL and tissuedigest eosinophil and neutrophil numbers as well as the lunghistopathology score.

[1006] (ii) Compounds of the invention were able to inhibitsignificantly the infiltration of neutrophils and eosinophils 24 hoursafter antigenic challenge compared to the non-drug treated controls asassessed in all three methods noted above. The dose range for efficacywas between 3 and 100 mg/kg po.

[1007] These results indicate that compounds of the inventiondemonstrate anti-inflammatory activity when given prophylacticlly in arat model of antigen induced leukocyte infiltration either orally orintraperitoneally.

[1008] 3. Inhibition of Acute Antigen Induced Bronchoconstriction in theAllergic Rat

[1009] Protocol for Sensitization and Challenge

[1010] Brown Norway rats were sensitized on days 0, 12 and 21 withovalbumin (100 μg, i.p) administered with aluminum hydroxide (100 mg,i.p). On the day of study the rats were surgically prepared for themeasurement of pulmonary mechanics and mechanically ventilated. After afive-minute equilibration period, the animals received a bolus ofovalbumin (1 mg per rat). The animals were then followed for 15 minutesand peak changes from base line resistance recorded as the response toantigen challenge.

[1011] Protocol for Dosing

[1012] Test drug was given either p.o. or i.p. 24 and 2 hours before theiv bolus injection of ovalbumin. The range of compound delivered inthese studies was 10-100 mg/kg po.

[1013] Results

[1014] Following antigen challenge in the non-drug treated andbudesonide control-treated animals there was a significant increase inthe airway resistance over baseline. In contrast, compounds of theinvention significantly inhibited the antigen-inducedbronchoconstriction.

[1015] These results indicate that compounds of the invention inhibitantigen-induced bronchoconstriction.

[1016] 4. Inhibition of Sephadex Induced Rat Lung Edema and CytokineGene Expression in the Allergic Rat

[1017] Protocol for Sephadex Administration

[1018] Male Sprague-Dawley rats (400 g), were dosed i.t. with vehicle(saline) or Sephadex (5 mg/kg) in a dose volume of 1 ml/kg underhalothane anesthesia (4% in oxygen for 3 min).

[1019] Protocol for Dosing

[1020] Drug was administered p.o. 1 hour before and 5 hours afterSephadex i.t in a dose volume of 1 ml/kg..

[1021] Protocol for Assessing Edema as an Endpoint

[1022] Twenty-four hours after Sephadex administration the animals weresacrificed with Euthatal (1 ml/kg i.p.), the heart and lungs removed enbloc. An increase in wet weight was used as an index of edema. The wetweight determined and then corrected for 100 g initial body weight.

[1023] Protocol for RT-PCR (Measurement of Cytokine Gene Expression)

[1024] RNA was isolated from lung tissue by a guanidiumthiocyanate-phenol-chloroform extraction technique. RNA was reversetranscribed to cDNA using AMV reverse transcriptase. cDNA for IL-5,IL-4, eotaxin and GAPDH (control gene) were amplified by PCR usingoligonucleotide sequences synthesized (Gibco) from published sequences.

[1025] The PCR reagents were overlaid with mineral oil and amplificationwas carried out through 25-35 cycles of denaturation at 95° C. for 1minute, annealing at 55-65° C. for 1 minute and extending at 72° C. for7 minutes. The PCR products, stained with ethidium bromide, wereelectrophoresed in 2% agarose gels to visualize cDNA bands.

[1026] Bands of each target fragment were visualized by ultraviolettransillumination and photographed. Photographs were scanned on adensitometer and integrated optical densities (OD×mm) of each band werecalculated by image analysis software (Imagemaster, Pharmacia). For eachanimal, the amount of each cytokine PCR product was normalized to theamount of GAPDH PCR product.

[1027] Results

[1028] (i) Sephadex instillation alone evoked a significant edema of 32%

[1029] (ii) Compounds of the invention inhibited the edema in a dosedependant manner by at doses of 10, 30 and 100 mg/kg

[1030] (iii) Sephadex caused an increased expression of the Th-2cytokines IL-4 and IL-5 together with the CC chemokine eotaxin in thelung 24 hours after challenge. There was a trend toward an increase inthe expression of IL-5 and eotaxin mRNA.

[1031] (iv) L-4 mRNA expression was dose dependently inhibited bycompounds of the invention.

[1032] Compounds of the invention inhibit Sephadex induced lung edema inthe rat, which is associated with a reduction in Sephadex induction ofIL-4.

[1033] 5. Inhibition of Antigen-induced Histamine Release in theAllergic Brown-Norway Rat

[1034] Protocol for Sensitization and Challenge

[1035] Brown Norway rats were sensitized on days 0, 12 and 21 withovalbumin (100 μg, i.p) administered with aluminum hydroxide (100 mg,i.p). On the day of study, the rats were surgically prepared for theinfusion of antigen. After a five-minute equilibration period, theanimals received a bolus of ovalbumin (1 mg per rat). Blood samples weretaken 2 minutes after ovalbumin challenge and plasma histamine levelswere measured using a histamine ELISA.

[1036] Protocol for Dosing

[1037] Test drug was given i.p. 30 min before ovalbumin challenge. Onlya single 30 mg/kg i.p. concentration was used in this study

[1038] Results

[1039] Following antigen challenge, the Syk Kinase inhibitorssignificantly inhibited the antigen-induced histamine release incomparison to the vehicle treated group.

[1040] These results indicate that compounds of the invention inhibitantigen-induced histamine release.

[1041] 6. Inhibition of ED-1+ Alveolar Macrophages in Rat Lung Tissue

[1042] Protocol for Sensitization and Challenge

[1043] Brown Norway rats were sensitized on days 0, 12 and 21 withovalbumin (100 μg, i.p) administered with aluminum hydroxide (100 mg,i.p). On day 30, the rats were exposed to a 1% aerosol of ovalbumin fora period of 30 minutes. The animals were then returned to housing.

[1044] Protocol for Dosing

[1045] Test drug was given either p.o. or i.p. 24 and 2 hours before theiv bolus injection of ovalbumin. The range of compound delivered inthese studies was 10-100 mg/kg po.

[1046] Protocol for EDI Quantification

[1047] Alveolar macrophages were quantified following immunostainingwith ED-1 antibody in paraffin-embedded lung tissue sections.

[1048] Results

[1049] (i) Ovalbumin challenge resulted in a 10-fold increase in thenumber of ED1+ macrophages in the alveolar bed.

[1050] (ii) Inhibition of Syk Kinase significantly reduced theovalbumin-induced increase in ED1 alveolar macrophages in adose-dependent manner.

[1051] Oral administration of compounds of the invention produced adose-related reduction in ED-1+ alveolar macrophages following ovalbuminchallenge.

[1052] 7. Inhibition of Antigen-induced Airway Neutrophilia in theBrown-Norway Rat

[1053] Protocol for Sensitization and Challenge

[1054] Brown Norway rats were sensitized on days 0, 12 and 21 withovalbumin (100 μg, i.p) administered with aluminum hydroxide (100 mg,i.p). On day 30, the rats were exposed to a 1% aerosol of ovalbumin fora period of 30 minutes. The animals were then returned to housing.

[1055] Protocol for Drug Dosing

[1056] One hour before antigen challenge, rats were dosed orally. Therange of compound delivered in these studies was 1-100 mg/kg po.

[1057] Protocol for Cell Analysis

[1058] Four hours after challenge, cells were recovered from the airwaylumen by bronchoalveolar lavage (RPMI/FCS as previously described).Immediately after lavage, lungs were perfused with RPMI/FCS to removethe blood pool of cells. 300 mg of tissue was chopped and cells wererecovered by enzymatic (collagenase) disaggregation. Differential cellcounts were made by light microscopy of stained cytocentrifugepreparations stained with Wright-Giemsa stain.

[1059] Results

[1060] (i) Four hours after antigen challenge a significant increase inneutrophils was observed in both the BAL and lung tissue.

[1061] (ii) The ovalbumin-induced increase in neutrophils in the BAL,but not the lung tissue, was significantly suppressed by compounds ofthe invention.

1. A pharmaceutical composition comprising an effective selective kinaseinhibitory amount of a compound of general formula (I):

wherein: R¹ represents aryl or heteroaryl each optionally substituted byone or more groups selected from acyl, alkylenedioxy, alkenyl,alkenyloxy, alkynyl, aryl, cyano, halo, hydroxy, heteroaryl,heterocycloalkyl, nitro, R⁴, —C(═O)—NY¹Y², —C(═O)—OR⁵, —NY¹Y²,—N(R⁶)—C(═O)—R⁷, —N(R⁶)—C(═O)—NY³Y⁴, —N(R⁶)—C(═O)—OR⁷, —N(R⁶)—SO₂—R⁷,—N(⁶)—SO₂—NY³Y⁴, —SO₂—NY¹Y² and —Z²R⁴; R² represents hydrogen, acyl,cyano, halo, lower alkenyl or lower alkyl optionally substituted by asubstituent selected from cyano, heteroaryl, heterocycloalkyl, —Z¹R⁸,—C(═O)—NY³Y⁴, —CO₂R⁸, —NY³Y⁴, —N(R⁶)—C(═O)—R⁷, —N(R⁶)—C(═O)—NY³Y⁴,—N(R⁶)—C(═O)—OR⁷, —N(R⁶)—SO₂—R⁷, —N(R⁶)—SO₂—NY³Y⁴ and one or morehalogen atoms; R³ represents hydrogen, aryl, cyano, halo, heteroaryl,lower alkyl, —C(═O)—OR⁵ or —C(═O)—NY³Y; R⁴ represents alkyl, cycloalkylor cycloalkylalkyl each optionally substituted by a substituent selectedfrom aryl, cycloalkyl, cyano, halo, heteroaryl, heterocycloalkyl, —CHO(or a 5-, 6- or 7-membered cyclic acetal derivative thereof),—C(═O)—NY¹Y², —C(═O)—OR⁵, —NY¹Y², —N(R⁶)—C(═O)—R⁷, —N(R⁶)—C(═O)—NY³Y⁴,—N(R⁶)—SO₂—R⁷, —N(R⁶)—SO₂—NY³Y⁴, —OR⁷ and one or more groups selectedfrom hydroxy and carboxy; R⁵ represents hydrogen, alkyl, alkenyl, aryl,arylalkyl, heteroaryl or heteroarylalkyl; R⁶ represents hydrogen orlower alkyl; R⁷ represents alkyl, aryl, arylalkyl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl orheterocycloalkylalkyl; R⁸ represents hydrogen or lower alkyl; X¹represents N, CH, C-halo, C—CN, C—R⁷, C—NY³Y⁴, C—OH, C—Z²R⁷,C—C(═O)—OR⁵, C—C(═O)—NY³Y⁴, C—N(R⁸)—C(═O)—R⁷, C—SO₂—NY³Y⁴,C—N(R⁸)—SO₂—R⁷, C-alkenyl, C-alkynyl or C—NO₂; Y¹ and Y² areindependently hydrogen, alkenyl, aryl, cycloalkyl, heteroaryl or alkyloptionally substituted by one or more groups selected from aryl, halo,heteroaryl, hydroxy, —C(═O)—NY³Y⁴, —C(═O)—OR⁵, —NY³Y⁴, —N(R⁶)—C(═O)—R⁷,—N(R⁶)—C(═O)—NY³Y⁴, —N(R⁶)—SO₂—R⁷, —N(R⁶)—SO₂—NY³Y⁴ and —OR⁷; or thegroup —NY¹Y² may form a cyclic amine; Y³ and Y⁴ are independentlyhydrogen, alkenyl, alkyl, aryl, arylalkyl, cycloalkyl, heteroaryl orheteroarylalkyl; or the group —NY³Y⁴ may form a cyclic amine; Z¹represents O or S; Z² represents O or S(O)_(n); n is zero or an integer1 or 2; and their corresponding N-oxides, and their prodrugs, and theiracid bioisosteres; and pharmaceutically acceptable salts and solvates(e.g. hydrates) of such compounds and their N-oxides and their prodrugs,and their acid bioisosteres; together with one or more pharmaceuticallyacceptable carriers or excipients.
 2. A compound of formula (I)according to claim 1, but excluding the compounds2-phenyl-1H-pyrrolo[2,3-b]pyridine,2-(4-bromo-phenyl)-3-methyl-1H-pyrrolo[2,3-b]pyridine,4-(3-methyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-benzoic acid methyl ester,2-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine,2-(4-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridine,5-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridine,4-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridine,2-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridine,4-(3-methyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-benzoic acid,2-(4-methoxy-phenyl)-3-methyl-1H-pyrrolo[2,3-b]pyridine,2-(4-methyl-phenyl)-3-methyl-1H-pyrrolo[2,3-b]pyridine,4-(3-methyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-benzoic acid isopropyl ester,2-phenyl-3-methyl-1H-pyrrolo[2,3-b]pyridine,6-phenyl-5H-pyrrolo[2,3-b]pyrazine,6-(4-methoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazine,6-(4-chloro-phenyl)-5H-pyrrolo[2,3-b]pyrazine,6-(2-chloro-phenyl)-5H-pyrrolo[2,3-b]pyrazine,3-methyl-6-phenyl-5H-pyrrolo[2,3-b]pyrazine,2-methyl-6-phenyl-5H-pyrrolo[2,3-b]pyrazine and7-methyl-6-phenyl-5H-pyrrolo[2,3-b]pyrazine.
 3. A compound according toclaim 2 in which R¹ is optionally substituted heteroaryl.
 4. A compoundaccording to claim 3 in which R¹ is optionally substitutedazaheteroaryl.
 5. A compound according to claim 2 in which R¹ isoptionally substituted indolyl, optionally substituted furanyl,optionally substituted pyridyl, optionally substituted pyrrolyl,optionally substituted pyrazolyl, optionally substituted quinolinyl,optionally substituted isoquinolinyl, optionally substituted imidazolyl,optionally substituted indazolyl, optionally substituted indolizinyl,optionally substituted tetrahydroindolizinyl or optionally substitutedindazolinyl.
 6. A compound according to any one of claims 3-5 in whichthe optionally substituents within R¹ are one or more groups selectedfrom alkylenedioxy, alkenyl, alkenyloxy, aryl, carboxy (or an acidbioisostere), cyano, halo, hydroxy, heteroaryl, heterocycloalkyl, R⁴,—C(═O)—R⁴, —C(═O)—NY¹Y², —C(═O)—OR⁵, —NY¹Y² and —OR⁴.
 7. A compoundaccording to claim 2 in which R¹ is optionally substituted aryl.
 8. Acompound according to claim 7 in which R¹ is phenyl substituted by oneor more groups selected from alkylenedioxy, halo, R⁴, —NY¹Y² and —OR⁴.9. A compound according to any one of claims 2-8 in which R² ishydrogen.
 10. A compound according to any one of claims 2-8 in which R²is halo.
 11. A compound according to any one of claims 2-8 in which R²is lower alkyl optionally substituted by carboxy, cyano, halo, hydroxy,tetrazolyl, or —CONY³Y⁴.
 12. A compound according to any one of claims2-8 in which R² is lower alkenyl.
 13. A compound according to any one ofclaims 2-12 in which R³ is hydrogen.
 14. A compound according to any oneof claims 2-12 in which R³ is optionally substituted aryl.
 15. Acompound according to any one of claims 2-12 in which R³ is optionallysubstituted phenyl.
 16. A compound according to any one of claims 2-12in which R³ is lower alkyl.
 17. A compound according to any one ofclaims 2-16 in which X¹ is N.
 18. A compound according to any one ofclaims 2-16 in which X¹ is CH.
 19. A compound according to any one ofclaims 2-16 in which X¹ is C-lower alkoxy.
 20. A compound according toany one of claims 2-16 in which X¹ is C-aryl.
 21. A compound accordingto any one of claims 2-16 in which X¹ is C—Cl.
 22. A compound accordingto any one of claims 2-16 in which X¹ is C—CN.
 23. A compound of formula(Ia):

in which R², R³ and X¹ are as hereinbefore defined in claim 1; R⁹ ishydrogen, R⁴, alkenyl or heterocycloalkyl; R¹⁰ is alkenyloxy, carboxy(or an acid bioisostere), cyano, halo, hydroxy, heteroaryl, R⁴,—C(═O)—R⁴, —C(═O)—NY¹Y², —OR⁴, —N(R⁶)—C(═O)—R⁷, —N(R⁶)—SO₂—R⁷ or —NY¹Y²;and p is zero, an integer 1 or 2; and their prodrugs andpharmaceutically acceptable salts, and solvates (e.g. hydrates) ofcompounds of formula (Ia) and their prodrugs.
 24. A compound accordingto claim 23 in which R² is hydrogen.
 25. A compound according to claim23 or 24 in which R³ is hydrogen, optionally substituted aryl or loweralkyl.
 26. A compound according to any one of claims 23 to 25 in whichX¹ is CH, C-lower alkoxy, C-aryl, C-halo, C—CN, or N.
 27. A compoundaccording to any one of claims 23 to 26 in which R⁹ is: (i) hydrogen;(ii) C₁₋₄alkyl; (iii) C₁₋₄alkyl substituted by hydroxy; (iv) C₁₋₄alkylsubstituted by —N(R⁶)C(═O)—R⁷; (v) C₁₋₄alkyl substituted by—C(═O)—NY¹Y²; or (vi) cycloalkylalkyl substituted by hydroxy.
 28. Acompound according to any one of claims 23 to 27 in which R¹⁰ is: (i)hydroxy; (ii) —OR⁴ in which R⁴ is alkyl; (iii) —OR⁴ in which R⁴ is alkylor cycloalkylalkyl, each substituted by one or more hydroxy groups; (iv)—OR⁴ in which R⁴ is alkyl substituted by one or more alkoxy groups; (v)—OR⁴ in which R⁴ is alkyl or cycloalkyl, each substituted by one or morecarboxy; (vi) —OR⁴ in which R⁴ is cycloalkyl substituted by—C(═O)—NY¹Y²; (vii) —N(R⁶)—C(═O)—R⁷; (viii) —CONY¹Y²; (ix) carboxy (x)alkyl substituted by carboxy; (xi) heteroaryl; (xii) —C(═O)—R⁴ in whichR⁴ is alkyl; or (xii) tetrazolyl or N-methyltetrazolyl;
 29. A compoundaccording to claim 28 in which R¹⁰ is attached to position 5 of theindolyl ring.
 30. A compound of formula (Ib):

in which R², R³, R⁹, R¹⁰, X¹ and p are as hereinbefore defined in claim23, and their prodrugs and pharmaceutically acceptable salts, andsolvates (e.g. hydrates) of compounds of formula (Ib) and theirprodrugs.
 31. A compound according to claim 30 in which R² is hydrogen.32. A compound according to claim 30 or 31 in which R³ is hydrogen,optionally substituted aryl or lower alkyl.
 33. A compound according toany one of claims 30 to 32 in which X¹ is CH, C-lower alkoxy, C-aryl,C-halo, C—CN, or N.
 34. A compound according to any one of claims 30 to33 in which R⁹ is hydrogen or C₁₋₄alkyl.
 35. A compound according to anyone of claims 30 to 34 in which p is zero.
 36. A compound of formula(Ic):

in which R², R³, R⁹, R¹⁰, X¹ and p are as hereinbefore defined in claim23, and their prodrugs and pharmaceutically acceptable salts, andsolvates (e.g. hydrates) of compounds of formula (Ic) and theirprodrugs.
 37. A compound according to claim 36 in which R² is hydrogen.38. A compound according to claim 36 or 37 in which R³ is hydrogen,optionally substituted aryl or lower alkyl.
 39. A compound according toany one of claims 36 to 38 in which X¹ is CH, C-lower alkoxy, C-aryl,C-halo, C—CN, or N.
 40. A compound according to any one of claims 36 to39 in which R⁹ is hydrogen or C₁₋₄alkyl.
 41. A compound according to anyone of claims 36 to 40 in which p is
 1. 42. A compound according to anyone of claims 36 to 41 in which R¹⁰ represents aryl.
 43. A compoundaccording to claim 42 in which R¹⁰ is attached at position 4 of thepyrrole ring.
 44. A compound of formula (Id):

in which R², R³, R¹⁰, X¹ and p are as hereinbefore defined in claim 23,and their prodrugs and pharmaceutically acceptable salts, and solvates(e.g. hydrates) of compounds of formula (Id) and their prodrugs.
 45. Acompound according to claim 44 in which R² is hydrogen, lower alkyl,lower alkyl substituted by —CONY³Y⁴, lower alkyl substituted by carboxy,lower alkyl substituted by tetrazolyl or lower alkyl substituted byhydroxy.
 46. A compound according to claims 44 or 45 in which R³ ishydrogen, optionally substituted aryl or lower alkyl.
 47. A compoundaccording to any one of claims 44 to 46 in which X¹ is CH, C-loweralkoxy, C-aryl, C-halo, C—CN, or N.
 48. A compound according to claimsany one of claims 44 to 47 in which p is
 1. 49. A compound according toany one of claims 44 to 48 in which R¹⁰ is alkyl.
 50. A compoundaccording to claim 49 in which R¹⁰ is attached at position 4 of thephenyl ring.
 51. A compound according to claim 2 selected from the groupconsisting of:6-(5-methoxy-1-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine;1-[1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indol-5-yloxy]-cyclobutanecarboxylicacid amide;2-(5-methoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile;{1-[1-methyl-3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-1H-indol-5-yloxy]-cyclobutyl}-methanol;and their prodrugs, and pharmaceutically acceptable salts and solvatesof such compounds and their prodrugs.
 52. A compound according to claim2 or a corresponding prodrug, or a pharmaceutically acceptable salt orsolvate of such a compound or a prodrug thereof, for use in therapy. 53.A compound according to claim 2 or a corresponding prodrug, or apharmaceutically acceptable salt or solvate of such a compound or aprodrug thereof, for use in the treatment of a patient suffering from,or subject to, conditions which can be ameliorated by the administrationof an inhibitor of the catalytic activity of Syk kinase.
 54. Acomposition according to claim 1 for use in the treatment of a patientsuffering from, or subject to, conditions which can be ameliorated bythe administration of an inhibitor of the catalytic activity of Sykkinase.
 55. A composition according to claim 1 for use in the treatmentof inflammatory diseases.
 56. A composition according to claim 1 for usein the treatment of asthma.
 57. A composition according to claim 1 foruse in the treatment of psoriasis.
 58. A composition according to claim1 for use in the treatment of joint inflammation.
 59. A compositionaccording to claim 1 for use in the treatment of inflammatory boweldisease.
 60. Use of a compound according to claim 2 or a correspondingprodrug, or a pharmaceutically acceptable salt or solvate of such acompound or a prodrug thereof, in the manufacture of a medicament forthe treatment of a patient suffering from, or subject to, conditionswhich can be ameliorated by the administration of an inhibitor of thecatalytic activity of Syk kinase.
 61. Use of a compound according toclaim 2 or a corresponding prodrug, or a pharmaceutically acceptablesalt or solvate of such a compound or a prodrug thereof, in themanufacture of a medicament for the treatment of asthma.
 62. Use of acompound according to claim 2 or a corresponding prodrug, or apharmaceutically acceptable salt or solvate of such a compound or aprodrug thereof, in the manufacture of a medicament for the treatment ofpsoriasis.
 63. Use of a compound according to claim 2 or a correspondingprodrug, or a pharmaceutically acceptable salt or solvate of such acompound or a prodrug thereof, in the manufacture of a medicament forthe treatment of joint inflammation.
 64. Use of a compound according toclaim 2 or a corresponding prodrug, or a pharmaceutically acceptablesalt or solvate of such a compound or a prodrug thereof, in themanufacture of a medicament for the treatment of inflammatory boweldisease.
 65. A method for the treatment of a human or non-human animalpatient suffering from, or subject to, conditions which can beameliorated by the administration to said patient of an inhibitor of Sykkinase—comprising administering to said patient an effective amount of acompound according to claim 2 or a corresponding prodrug, or apharmaceutically acceptable salt or solvate of such a compound or aprodrug thereof.
 66. A compound substantially as hereinbefore describedwith references to the Examples.